NM_020937.4(FANCM):c.1466T>C (p.Val489Ala) AND Fanconi anemia

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 6, 2019
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:: RCV001211503.6

Allele description

NM_020937.4(FANCM):c.1466T>C (p.Val489Ala)

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.1466T>C (p.Val489Ala)

HGVS:

NC_000014.9:g.45159165T>C
NG_007417.1:g.28233T>C
NM_001308133.2:c.1388T>C
NM_001308134.2:c.1466T>C
NM_020937.4:c.1466T>CMANE SELECT
NP_001295062.1:p.Val463Ala
NP_001295063.1:p.Val489Ala
NP_065988.1:p.Val489Ala
LRG_502t1:c.1466T>C
LRG_502:g.28233T>C
NC_000014.8:g.45628368T>C
NM_020937.2:c.1466T>C

Protein change:

V463A

Links:

dbSNP: rs1887401440

NCBI 1000 Genomes Browser:

rs1887401440

Molecular consequence:

NM_001308133.2:c.1388T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001308134.2:c.1466T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020937.4:c.1466T>C - 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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PREDICTED: Homo sapiens peroxisomal biogenesis factor 14 (PEX14), transcript var...
PREDICTED: Homo sapiens peroxisomal biogenesis factor 14 (PEX14), transcript variant X4, mRNA
gi|2462510047|ref|XM_054337016.1|

Nucleotide
PREDICTED: Homo sapiens peroxisomal biogenesis factor 14 (PEX14), transcript var...
PREDICTED: Homo sapiens peroxisomal biogenesis factor 14 (PEX14), transcript variant X3, mRNA
gi|2462510045|ref|XM_054337015.1|

Nucleotide
mitochondrial import inner membrane translocase subunit Tim9 isoform d [Homo sap...
mitochondrial import inner membrane translocase subunit Tim9 isoform d [Homo sapiens]
gi|751358960|ref|NP_001291420.1|

Protein
Roseburia intestinalis L1-82 Scfld102, whole genome shotgun sequence
Roseburia intestinalis L1-82 Scfld102, whole genome shotgun sequence
gi|242364176|ref|NZ_GG692814.1||gnl NZ_ABYJ02|Scfld102

Nucleotide
Roseburia intestinalis L1-82 Scfld85, whole genome shotgun sequence
Roseburia intestinalis L1-82 Scfld85, whole genome shotgun sequence
gi|242364160|ref|NZ_GG692798.1||gnl NZ_ABYJ02|Scfld85

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001383044	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 6, 2019)	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

SCV001383044

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 6, 2019)

germline

clinical testing

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

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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 Invitae, SCV001383044.5

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

Description

This variant is not present in population databases (ExAC no frequency). 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FANCM-related conditions. This sequence change replaces valine with alanine at codon 489 of the FANCM protein (p.Val489Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine.

#	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: Feb 28, 2024

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