NM_000135.4(FANCA):c.353C>T (p.Ala118Val) AND Fanconi anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 26, 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:: RCV000804007.4

Allele description [Variation Report for NM_000135.4(FANCA):c.353C>T (p.Ala118Val)]

NM_000135.4(FANCA):c.353C>T (p.Ala118Val)

Gene:

FANCA:FA complementation group A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000135.4(FANCA):c.353C>T (p.Ala118Val)

HGVS:

NC_000016.10:g.89811002G>A
NG_011706.1:g.10656C>T
NM_000135.4:c.353C>TMANE SELECT
NM_001018112.3:c.353C>T
NM_001286167.3:c.353C>T
NM_001351830.2:c.353C>T
NP_000126.2:p.Ala118Val
NP_001018122.1:p.Ala118Val
NP_001273096.1:p.Ala118Val
NP_001338759.1:p.Ala118Val
LRG_495t1:c.353C>T
LRG_495:g.10656C>T
NC_000016.9:g.89877410G>A
NM_000135.2:c.353C>T

Protein change:

A118V

Links:

dbSNP: rs1201642328

NCBI 1000 Genomes Browser:

rs1201642328

Molecular consequence:

NM_000135.4:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001018112.3:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001286167.3:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351830.2:c.353C>T - 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

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leucine-rich repeat-containing protein 45 [Homo sapiens]
leucine-rich repeat-containing protein 45 [Homo sapiens]
gi|21450705|ref|NP_659436.1|

Protein
LOC130067958 [Homo sapiens]
LOC130067958 [Homo sapiens]
Gene ID:130067958

Gene
LOC130067973 [Homo sapiens]
LOC130067973 [Homo sapiens]
Gene ID:130067973

Gene
atp5po.S ATP synthase peripheral stalk subunit OSCP S homeolog [Xenopus laevis]
atp5po.S ATP synthase peripheral stalk subunit OSCP S homeolog [Xenopus laevis]
Gene ID:446923

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000943897	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 26, 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

SCV000943897

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 26, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000943897.3

#	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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 118 of the FANCA protein (p.Ala118Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 649143). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FANCA protein function. 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: Sep 29, 2024

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