Variant Detail

Variant Information
ID
DPV: 10183
Chromosome
11
Gene
HGVS (GRCh37/hg19)
NC_000011.9:g.108014766G>C
HGVS (GRCh38/hg38)
NC_000011.10:g.108144039G>C
HGVS (RNA)
NM_000019.3:c.997G>C
HGVS (Protein)
NP_000010.1:p.A333P
dbSNP
-
ClinGen Allele Registry
CA252471
Allele Frequency
Individual Information

ID
DPVS:11485.2
Clinical Significance
Pathogenic
Date Last Evaluated
2019-07-21
Clinical Significance Citation
Hori, T. Inborn errors of ketone body utilization. 2015 Pediatr Int. 2015;57(1):41-8. doi: 10.1111/ped.12585. PMID:25559898
Fukao, T. Ketone body metabolism and its defects. 2014 J Inherit Metab Dis. 2014 Jul;37(4):541-51. doi: 10.1007/s10545-014-9704-9. Epub 2014 Apr 8. PMID:24706027
Fukao, T. The mitochondrial acetoacetyl-CoA thiolase (T2) deficiency in Japanese patients: urinary organic acid and blood acylcarnitine profiles under stable conditions have subtle abnormalities in T2-deficient patients with some residual T2 activity. 2003 J Inherit Metab Dis. 2003;26(5):423-31. doi: 10.1023/a:1025117226051. PMID:14518824

Transcript
  • NM_000019.3:c.997G>C
Disease

Phenotype
-
Zygosity
compound heterozygote
Allele Origin
maternal
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • SEQuencing
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
c.[149delC];[997G>C]

ID
DPVS:12384.1
Clinical Significance
Pathogenic
Date Last Evaluated
2020-01-08
Clinical Significance Citation
Fukao, T. Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency. 1998 Hum Mutat. 1998;12(4):245-54. doi: 10.1002/(SICI)1098-1004(1998)12:4<245::AID-HUMU5>3.0.CO;2-E. PMID:9744475
Hiyama, K. Deficient beta-ketothiolase activity in leukocytes from a patient with 2-methylacetoacetic aciduria. 1986 Clin Chim Acta. 1986 Mar 16;155(2):189-94. doi: 10.1016/0009-8981(86)90283-4. PMID:3698316

Transcript
-
Disease

Phenotype
-
Zygosity
compound heterozygote
Allele Origin
maternal
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • HeteroDuplex analysis
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
c.[149delC];[997G>C]

ID
DPVS:12419.1
Clinical Significance
Pathogenic
Date Last Evaluated
2020-01-08
Clinical Significance Citation
Fukao, T. Molecular basis of beta-ketothiolase deficiency: mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene. 1995 Hum Mutat. 1995;5(2):113-20. doi: 10.1002/humu.1380050203. PMID:7749408
Fukao, T. Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency. 1998 Hum Mutat. 1998;12(4):245-54. doi: 10.1002/(SICI)1098-1004(1998)12:4<245::AID-HUMU5>3.0.CO;2-E. PMID:9744475

Transcript
-
Disease

Phenotype
-
Zygosity
compound heterozygote
Allele Origin
germline
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • SEQuencing
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
c.[149delC];[997G>C]

ClinVar
Model Animals
VCF
VCF (GRCh37/hg19) 
											##fileformat=VCFv4.0
##reference=GRCh37
##INFO=<ID=CLNALLELEID,Number=1,Type=Integer,Description="the ClinVar Allele ID">
##INFO=<ID=CLNDISDB,Number=.,Type=String,Description="Tag-value pairs of disease database name and identifier, e.g. OMIM:NNNNNN (from ClinVar)">
##INFO=<ID=CLNDN,Number=.,Type=String,Description="ClinVar's preferred disease name for the concept specified by disease identifiers in CLNDISDB (from ClinVar)">
##INFO=<ID=CLNHGVS,Number=.,Type=String,Description="Top-level (primary assembly, alt, or patch) HGVS expression.(from ClinVar)">
##INFO=<ID=CLNSIG,Number=.,Type=String,Description="Clinical significance for this single variant (from ClinVar)">
##INFO=<ID=EXAC_AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed (from ExAC r1)">
##INFO=<ID=EXAC_AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed (from ExAC r1)">
##INFO=<ID=EXAC_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from ExAC r1)">
##INFO=<ID=EXAC_FILTER,Number=1,Type=String,Description="calculated by self of overlapping values in field FILTER (from ExAC r1)">
##INFO=<ID=GNOMAD_AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from gnomAD v2.1.1 )">
##INFO=<ID=HGVD_AAF,Number=A,Type=Float,Description="Alternative Allele Frequency(s) NA/(NR+NAtotal) (from HGVD/DBexome20170802)">
##INFO=<ID=HGVD_AC,Number=A,Type=Integer,Description="number(s) of alternative allele(s) (from HGVD/DBexome20170802)">
##INFO=<ID=HGVD_NR,Number=1,Type=Integer,Description="number of reference allele (from HGVD/DBexome20170802)">
##INFO=<ID=TOMMO_4_7K_AC,Number=A,Type=Integer,Description="Allele count in genotypes (from ToMMo 4.7KJPN (20190826))">
##INFO=<ID=TOMMO_4_7K_AF,Number=A,Type=Float,Description="Allele frequency, for each ALT allele, in the same order as listed  (from ToMMo 4.7KJPN (20190826))">
##INFO=<ID=TOMMO_4_7K_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from ToMMo 4.7KJPN (20190826))">
##INFO=<ID=dbSNP_RSID,Number=1,Type=String,Description="dbSNP ID (from dbSNP b151 )">
##INFO=<ID=GENEINFO,Number=1,Type=String,Description="Pairs each of gene symbol:gene id. The gene symbol and id are delimited by a colon (:)">
##INFO=<ID=DPVID,Number=.,Type=String,Description="DPV Variant ID">
##INFO=<ID=DPVSIG,Number=.,Type=String,Description="Variant Clinical Significance">
##INFO=<ID=DPVDSDBID,Number=.,Type=String,Description="Variant disease database ID">
##INFO=<ID=DPVDBN,Number=.,Type=String,Description="Variant disease name">
##INFO=<ID=DPVHGVS,Number=.,Type=String,Description="Variant in HGVS.">
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
11	108014766	NC_000011.9:g.108014766G>C	G	C	.	.	TOMMO_4_7K_AF=0.0003;TOMMO_4_7K_AC=3;TOMMO_4_7K_AN=9544;CLNALLELEID=17884;CLNDN=Deficiency_of_acetyl-CoA_acetyltransferase;CLNDISDB=MONDO:MONDO:0008760,MedGen:C1536500,OMIM:203750,Orphanet:ORPHA134,SNOMED_CT:124258007;CLNSIG=Pathogenic/Likely_pathogenic;CLNHGVS=NC_000011.9:g.108014766G>C;GENEINFO=93:38;DPVID=10183;DPVSIG=Pathogenic;DPVDSDBID=OMIM:203750;DPVDBN=3-ketothiolase_deficiency;DPVHGVS=NC_000011.9:g.108014766G>C	.
VCF (GRCh38/hg38) 
											##fileformat=VCFv4.0
##reference=GRCh38
##INFO=<ID=CLNALLELEID,Number=1,Type=Integer,Description="the ClinVar Allele ID">
##INFO=<ID=CLNDISDB,Number=.,Type=String,Description="Tag-value pairs of disease database name and identifier, e.g. OMIM:NNNNNN (from ClinVar)">
##INFO=<ID=CLNDN,Number=.,Type=String,Description="ClinVar's preferred disease name for the concept specified by disease identifiers in CLNDISDB (from ClinVar)">
##INFO=<ID=CLNHGVS,Number=.,Type=String,Description="Top-level (primary assembly, alt, or patch) HGVS expression.(from ClinVar)">
##INFO=<ID=CLNSIG,Number=.,Type=String,Description="Clinical significance for this single variant (from ClinVar)">
##INFO=<ID=GNOMAD_AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from gnomAD v2.1.1 )">
##INFO=<ID=dbSNP_RSID,Number=1,Type=String,Description="dbSNP ID (from dbSNP b151 )">
##originalFile=</tmp/crossmap-input-8knxvngb>
##targetRefGenome=</usr/lib64/python2.7/site-packages/transvar/transvar.download/hg38.fa>
##INFO=<ID=GENEINFO,Number=1,Type=String,Description="Pairs each of gene symbol:gene id. The gene symbol and id are delimited by a colon (:)">
##INFO=<ID=DPVID,Number=.,Type=String,Description="DPV Variant ID">
##INFO=<ID=DPVSIG,Number=.,Type=String,Description="Variant Clinical Significance">
##INFO=<ID=DPVDSDBID,Number=.,Type=String,Description="Variant disease database ID">
##INFO=<ID=DPVDBN,Number=.,Type=String,Description="Variant disease name">
##INFO=<ID=DPVHGVS,Number=.,Type=String,Description="Variant in HGVS.">
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
11	108144039	NC_000011.9:g.108014766G>C	G	C	.	.	dbSNP_RSID=rs120074147;CLNALLELEID=17884;CLNDN=Deficiency_of_acetyl-CoA_acetyltransferase;CLNDISDB=MONDO:MONDO:0008760,MedGen:C1536500,OMIM:203750,Orphanet:ORPHA134,SNOMED_CT:124258007;CLNSIG=Pathogenic/Likely_pathogenic;CLNHGVS=NC_000011.10:g.108144039G>C;GENEINFO=93:38;DPVID=10183;DPVSIG=Pathogenic;DPVDSDBID=OMIM:203750;DPVDBN=3-ketothiolase_deficiency;DPVHGVS=NC_000011.10:g.108144039G>C	.