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NM_020937.4(FANCM):c.4366C>T (p.Arg1456Cys) AND Fanconi anemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 1, 2024
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:
RCV000378941.16

Allele description [Variation Report for NM_020937.4(FANCM):c.4366C>T (p.Arg1456Cys)]

NM_020937.4(FANCM):c.4366C>T (p.Arg1456Cys)

Gene:
FANCM:FA complementation group M [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q21.2
Genomic location:
Preferred name:
NM_020937.4(FANCM):c.4366C>T (p.Arg1456Cys)
HGVS:
  • NC_000014.9:g.45181685C>T
  • NG_007417.1:g.50753C>T
  • NM_001308133.2:c.4288C>T
  • NM_020937.4:c.4366C>TMANE SELECT
  • NP_001295062.1:p.Arg1430Cys
  • NP_065988.1:p.Arg1456Cys
  • LRG_502t1:c.4366C>T
  • LRG_502:g.50753C>T
  • NC_000014.8:g.45650888C>T
  • NM_020937.2:c.4366C>T
  • NM_020937.3:c.4366C>T
Protein change:
R1430C
Links:
dbSNP: rs200360968
NCBI 1000 Genomes Browser:
rs200360968
Molecular consequence:
  • NM_001308133.2:c.4288C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020937.4:c.4366C>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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000547798Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Feb 1, 2024)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV000547798.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1456 of the FANCM protein (p.Arg1456Cys). This variant is present in population databases (rs200360968, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID: 313218). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024