VCV000031129.23 - ClinVar

NM_001198800.3(ASCC1):c.869A>G (p.Asn290Ser)

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.

(6)

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.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001198800.3(ASCC1):c.869A>G (p.Asn290Ser)

Variation ID: 31129 Accession: VCV000031129.23

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q22.1 10: 72133059 (GRCh38) [ NCBI UCSC ] 10: 73892817 (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	Apr 4, 2013	Oct 20, 2024	Jan 11, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001198800.3:c.869A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001185729.1:p.Asn290Ser	missense
NM_001198798.2:c.869A>G	NP_001185727.1:p.Asn290Ser	missense
NM_001198799.3:c.953A>G	NP_001185728.1:p.Asn318Ser	missense
NM_001369085.1:c.935A>G	NP_001356014.1:p.Asn312Ser	missense
NM_001369086.1:c.935A>G	NP_001356015.1:p.Asn312Ser	missense
NM_001369087.1:c.869A>G	NP_001356016.1:p.Asn290Ser	missense
NM_001369088.1:c.869A>G	NP_001356017.1:p.Asn290Ser	missense
NM_001369089.1:c.869A>G	NP_001356018.1:p.Asn290Ser	missense
NM_001369090.1:c.869A>G	NP_001356019.1:p.Asn290Ser	missense
NM_001369091.1:c.869A>G	NP_001356020.1:p.Asn290Ser	missense
NM_001369092.1:c.869A>G	NP_001356021.1:p.Asn290Ser	missense
NM_001369093.1:c.869A>G	NP_001356022.1:p.Asn290Ser	missense
NM_001369094.1:c.869A>G	NP_001356023.1:p.Asn290Ser	missense
NM_001369095.1:c.869A>G	NP_001356024.1:p.Asn290Ser	missense
NM_001369096.1:c.869A>G	NP_001356025.1:p.Asn290Ser	missense
NM_001369097.1:c.869A>G	NP_001356026.1:p.Asn290Ser	missense
NM_001369098.1:c.869A>G	NP_001356027.1:p.Asn290Ser	missense
NM_001369099.1:c.815A>G	NP_001356028.1:p.Asn272Ser	missense
NM_001369100.1:c.749A>G	NP_001356029.1:p.Asn250Ser	missense
NM_001369101.1:c.752A>G	NP_001356030.1:p.Asn251Ser	missense
NM_001369102.1:c.752A>G	NP_001356031.1:p.Asn251Ser	missense
NM_001369103.1:c.749A>G	NP_001356032.1:p.Asn250Ser	missense
NM_001369104.1:c.749A>G	NP_001356033.1:p.Asn250Ser	missense
NM_001369105.1:c.752A>G	NP_001356034.1:p.Asn251Ser	missense
NM_001369106.1:c.752A>G	NP_001356035.1:p.Asn251Ser	missense
NM_001369107.1:c.752A>G	NP_001356036.1:p.Asn251Ser	missense
NM_001369108.1:c.749A>G	NP_001356037.1:p.Asn250Ser	missense
NM_001369109.1:c.749A>G	NP_001356038.1:p.Asn250Ser	missense
NM_001369110.1:c.869A>G	NP_001356039.1:p.Asn290Ser	missense
NM_001369111.1:c.869A>G	NP_001356040.1:p.Asn290Ser	missense
NM_001369112.1:c.749A>G	NP_001356041.1:p.Asn250Ser	missense
NR_045564.1:n.1216A>G		non-coding transcript variant
NC_000010.11:g.72133059T>C
NC_000010.10:g.73892817T>C
NG_031890.1:g.89076A>G
	Q8N9N2:p.Asn318Ser

... more HGVS ... less HGVS

Protein change

N290S, N318S, N272S, N250S, N251S, N312S

Other names

Canonical SPDI

NC_000010.11:72133058:T:C

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.

0.00100 (C)

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

1000 Genomes Project 0.00100

1000 Genomes Project 30x 0.00109

Exome Aggregation Consortium (ExAC) 0.00117

The Genome Aggregation Database (gnomAD), exomes 0.00117

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00123

Trans-Omics for Precision Medicine (TOPMed) 0.00129

The Genome Aggregation Database (gnomAD) 0.00135

Links

ClinGen: CA129699 UniProtKB: Q8N9N2#VAR_066588 OMIM: 614215.0001 dbSNP: rs146370051 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.
ASCC1		-	-	GRCh38 GRCh37	182	198

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.
Barrett esophagus/esophageal adenocarcinoma	Pathogenic (1)	no assertion criteria provided	Jul 27, 2011	RCV000024125.3
not specified	Likely benign (1)	criteria provided, single submitter	Aug 7, 2018	RCV000714753.3
Spinal muscular atrophy with congenital bone fractures 2	Benign (1)	criteria provided, single submitter	May 28, 2019	RCV000988384.1
not provided	Likely benign (3)	criteria provided, multiple submitters, no conflicts	Jan 11, 2024	RCV000885821.18

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.
Likely benign (Aug 07, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: inherited	Genomic Research Center, Shahid Beheshti University of Medical Sciences Accession: SCV000845481.1 First in ClinVar: Nov 03, 2018 Last updated: Nov 03, 2018	Number of individuals with the variant: 1 Sex: female Geographic origin: Iran
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Spinal muscular atrophy with congenital bone fractures 2 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001138084.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Likely benign (Jan 11, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001029293.5 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005221191.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Likely benign (Sep 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004126767.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: ASCC1: BP4 Number of individuals with the variant: 2
Pathogenic (Jul 27, 2011)	no assertion criteria provided Method: literature only	BARRETT ESOPHAGUS/ESOPHAGEAL ADENOCARCINOMA Affected status: not provided Allele origin: germline	OMIM Accession: SCV000045416.2 First in ClinVar: Apr 04, 2013 Last updated: Jan 06, 2020	Publications: PubMed (1) PubMed: 21791690 Comment on evidence: Orloff et al. (2011) identified a germline 869G-A transition in exon 8 of the ASCC1 gene, resulting in an asn290-to-ser (N290S) substitution, in 2 (2.1%) … (more) Orloff et al. (2011) identified a germline 869G-A transition in exon 8 of the ASCC1 gene, resulting in an asn290-to-ser (N290S) substitution, in 2 (2.1%) of 116 patients of European descent with Barrett esophagus and/or esophageal adenocarcinoma (614266). The mutation was not found in 125 controls. This genomic region was studied after being identified by genomewide linkage analysis of 21 concordant and 11 discordant sib pairs with the disorders. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma.	Orloff M	JAMA	2011	PMID: 21791690

Text-mined citations for rs146370051 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_001198800.3(ASCC1):c.869A>G (p.Asn290Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs146370051 ...