VCV000241697.40 - ClinVar

NM_032444.4(SLX4):c.5501A>G (p.Asn1834Ser)

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.

(12)

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.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(3); Likely benign(7)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_032444.4(SLX4):c.5501A>G (p.Asn1834Ser)

Variation ID: 241697 Accession: VCV000241697.40

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16p13.3 16: 3582346 (GRCh38) [ NCBI UCSC ] 16: 3632347 (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	Oct 2, 2016	Oct 20, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_032444.4:c.5501A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_115820.2:p.Asn1834Ser	missense
NM_032444.3:c.5501A>G
NC_000016.10:g.3582346T>C
NC_000016.9:g.3632347T>C
NG_028123.1:g.34239A>G
NG_033123.1:g.46A>G
LRG_503:g.34239A>G
LRG_503t1:c.5501A>G
	Q8IY92:p.Asn1834Ser

... more HGVS ... less HGVS

Protein change

N1834S

Other names

Canonical SPDI

NC_000016.10:3582345: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.

0.00200 (C)

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

1000 Genomes Project 0.00200

1000 Genomes Project 30x 0.00234

Trans-Omics for Precision Medicine (TOPMed) 0.00547

Exome Aggregation Consortium (ExAC) 0.00554

The Genome Aggregation Database (gnomAD), exomes 0.00558

The Genome Aggregation Database (gnomAD) 0.00575

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00585

Links

ClinGen: CA7865286 UniProtKB: Q8IY92#VAR_069017 dbSNP: rs111738042 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.
SLX4		-	-	GRCh38 GRCh37	2173	2235

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.
not specified	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Apr 19, 2017	RCV000243677.18
not provided	Conflicting interpretations of pathogenicity (4)	criteria provided, conflicting classifications	Aug 1, 2024	RCV000440447.20
Fanconi anemia	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV001086807.9
Fanconi anemia complementation group P	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jul 7, 2023	RCV001121536.9

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 (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000314947.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Nov 14, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000597129.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Likely benign (Apr 19, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not Specified Affected status: unknown Allele origin: germline	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital Accession: SCV000864327.1 First in ClinVar: Jan 22, 2019 Last updated: Jan 22, 2019	Comment: BS1,BP4,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction … (more) BS1,BP4,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). (less)
Likely benign (Jan 12, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Fanconi anemia complementation group P Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001280163.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
Likely benign (Mar 29, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001795002.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021	Comment: This variant is associated with the following publications: (PMID: 28051113, 28717660, 22401137, 28202063, 21805310)
Uncertain significance (Nov 03, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden Accession: SCV002009257.3 First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Fanconi anemia complementation group P Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004015491.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Fanconi anemia Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000291096.10 First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024
Likely benign (Aug 01, 2024)	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: SCV004144886.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: SLX4: BP4, BS2 Number of individuals with the variant: 42
Likely Benign (Jul 21, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000511742.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Comment: Converted during submission to Likely benign.
Likely benign (Mar 02, 2021)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Fanconi anemia Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002529385.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Likely benign (Aug 31, 2012)	no assertion criteria provided Method: curation	not specified Affected status: yes Allele origin: germline	Leiden Open Variation Database Accession: SCV001364707.1 First in ClinVar: Jun 27, 2020 Last updated: Jun 27, 2020	Publications: PubMed (1) PubMed: 22911665 Comment: Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker.
click to load more click to collapse

Comment:

BS1,BP4,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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
Analysis of the novel fanconi anemia gene SLX4/FANCP in familial breast cancer cases.	Bakker JL	Human mutation	2013	PMID: 22911665

Text-mined citations for rs111738042 ...

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_032444.4(SLX4):c.5501A>G (p.Asn1834Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs111738042 ...