NM_000136.3(FANCC):c.349G>A (p.Val117Ile) AND Fanconi anemia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 21, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001835817.3

Allele description [Variation Report for NM_000136.3(FANCC):c.349G>A (p.Val117Ile)]

NM_000136.3(FANCC):c.349G>A (p.Val117Ile)

Gene:

FANCC:FA complementation group C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.349G>A (p.Val117Ile)

HGVS:

NC_000009.12:g.95172144C>T
NG_011707.1:g.150566G>A
NM_000136.3:c.349G>AMANE SELECT
NM_001243743.2:c.349G>A
NM_001243744.2:c.349G>A
NP_000127.2:p.Val117Ile
NP_001230672.1:p.Val117Ile
NP_001230673.1:p.Val117Ile
LRG_497t1:c.349G>A
LRG_497:g.150566G>A
NC_000009.11:g.97934426C>T
NM_000136.2:c.349G>A

Protein change:

V117I

Links:

dbSNP: rs781167993

NCBI 1000 Genomes Browser:

rs781167993

Molecular consequence:

NM_000136.3:c.349G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243743.2:c.349G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243744.2:c.349G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Fanconi anemia (FA)
Synonyms:: Fanconi pancytopenia; Fanconi's anemia
Identifiers:: MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

Recent activity

Clear Turn Off Turn On

conserved membrane hypothetical protein [Thiomonas sp. CB3]
conserved membrane hypothetical protein [Thiomonas sp. CB3]
gi|1026941785|emb|CQR41311.1||gnl|W RM|CQR41311

Protein
Homologene neighbors for GEO Profiles (Select 132350957) (0)
GEO Profiles
Homologene neighbors for GEO Profiles (Select 131945171) (0)
GEO Profiles
Homologene neighbors for GEO Profiles (Select 23674766) (0)
GEO Profiles
Homologene neighbors for GEO Profiles (Select 23674272) (0)
GEO Profiles

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002081279	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 22, 2018)	germline	clinical testing
SCV003273431	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 21, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002081279

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 22, 2018)

germline

clinical testing

SCV003273431

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 21, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Natera, Inc., SCV002081279.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003273431.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 117 of the FANCC protein (p.Val117Ile). This variant is present in population databases (rs781167993, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 421810). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine