VCV001805706.3 - ClinVar

NM_000019.4(ACAT1):c.369_372del (p.Asn123fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(3)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000019.4(ACAT1):c.369_372del (p.Asn123fs)

Variation ID: 1805706 Accession: VCV001805706.3

Type and length

Deletion, 4 bp

Location

Cytogenetic: 11q22.3 11: 108135173-108135176 (GRCh38) [ NCBI UCSC ] 11: 108005900-108005903 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 24, 2022	Aug 25, 2024	Oct 12, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000019.4:c.369_372del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000010.1:p.Asn123fs	frameshift
NM_000019.3:c.369_372del
NM_001386677.1:c.369_372del	NP_001373606.1:p.Asn123fs	frameshift
NM_001386678.1:c.120+3222_120+3225del		intron variant
NM_001386679.1:c.72_75del	NP_001373608.1:p.Asn24fs	frameshift
NM_001386681.1:c.99_102del	NP_001373610.1:p.Asn33fs	frameshift
NM_001386682.1:c.99_102del	NP_001373611.1:p.Asn33fs	frameshift
NM_001386685.1:c.99_102del	NP_001373614.1:p.Asn33fs	frameshift
NM_001386686.1:c.99_102del	NP_001373615.1:p.Asn33fs	frameshift
NM_001386687.1:c.99_102del	NP_001373616.1:p.Asn33fs	frameshift
NM_001386688.1:c.99_102del	NP_001373617.1:p.Asn33fs	frameshift
NM_001386689.1:c.99_102del	NP_001373618.1:p.Asn33fs	frameshift
NM_001386690.1:c.99_102del	NP_001373619.1:p.Asn33fs	frameshift
NM_001386691.1:c.99_102del	NP_001373620.1:p.Asn33fs	frameshift
NR_170162.1:n.409_412del		non-coding transcript variant
NC_000011.10:g.108135176_108135179del
NC_000011.9:g.108005903_108005906del
NG_009888.2:g.23472_23475del
LRG_1400:g.23472_23475del
LRG_1400t1:c.369_372del	LRG_1400p1:p.Asn123fs

... more HGVS ... less HGVS

Protein change

N123fs, N24fs, N33fs

Other names

Canonical SPDI

NC_000011.10:108135172:AAACAAA:AAA

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ACAT1		-	-	GRCh38 GRCh37	734	759

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Deficiency of acetyl-CoA acetyltransferase	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Oct 12, 2023	RCV002472124.3
not provided	Likely pathogenic (1)	criteria provided, single submitter	Jul 13, 2022	RCV004697231.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 21, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Deficiency of acetyl-CoA acetyltransferase (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute Additional submitter: Shariant Australia, Australian Genomics Accession: SCV002768543.1 First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022	Publications: PubMed (2) PubMed: 29402417‚ 31268215 Comment: Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease … (more) Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 5 of 12). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0701 - Comparable variants also predicted to result in NMD, have very strong previous evidence for pathogenicity in patients with mitochondrial acetoacetyl‐CoA thiolase (T2) deficiency (PMID: 31268215, Decipher, ClinVar). (P) 0803 - Low previous evidence of pathogenicity in a homozygous individual with beta-ketothiolase deficiency (PMID: 31268215). (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign (less)
Pathogenic (Oct 12, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Deficiency of acetyl-CoA acetyltransferase Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004210453.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
Likely pathogenic (Jul 13, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, Skane University Hospital Lund Accession: SCV005197675.1 First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024

Comment:

Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 5 of 12). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0701 - Comparable variants also predicted to result in NMD, have very strong previous evidence for pathogenicity in patients with mitochondrial acetoacetyl‐CoA thiolase (T2) deficiency (PMID: 31268215, Decipher, ClinVar). (P) 0803 - Low previous evidence of pathogenicity in a homozygous individual with beta-ketothiolase deficiency (PMID: 31268215). (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mutation update on ACAT1 variants associated with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency.	Abdelkreem E	Human mutation	2019	PMID: 31268215
A novel method for quantitation of acylglycines in human dried blood spots by UPLC-tandem mass spectrometry.	Fisher L	Clinical biochemistry	2018	PMID: 29402417

Text-mined citations for this variant ...

Record last updated Aug 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000019.4(ACAT1):c.369_372del (p.Asn123fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...