NM_000135.4(FANCA):c.4155G>C (p.Glu1385Asp) AND Fanconi anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 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:: RCV001060791.8

Allele description [Variation Report for NM_000135.4(FANCA):c.4155G>C (p.Glu1385Asp)]

NM_000135.4(FANCA):c.4155G>C (p.Glu1385Asp)

Genes:

FANCA:FA complementation group A [Gene - OMIM - HGNC]
ZNF276:zinc finger protein 276 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000135.4(FANCA):c.4155G>C (p.Glu1385Asp)

HGVS:

NC_000016.10:g.89739145C>G
NG_011706.1:g.82513G>C
NM_000135.4:c.4155G>CMANE SELECT
NM_001113525.2:c.*899C>GMANE SELECT
NM_001286167.3:c.4155G>C
NM_152287.4:c.*899C>G
NP_000126.2:p.Glu1385Asp
NP_000126.2:p.Glu1385Asp
NP_001273096.1:p.Glu1385Asp
LRG_495t1:c.4155G>C
LRG_495:g.82513G>C
LRG_495p1:p.Glu1385Asp
NC_000016.9:g.89805553C>G
NM_000135.2:c.4155G>C
NR_110122.2:n.2899C>G
NR_110126.2:n.2782C>G
NR_110128.2:n.2722C>G
NR_110129.2:n.2816C>G

Protein change:

E1385D

Links:

dbSNP: rs770551622

NCBI 1000 Genomes Browser:

rs770551622

Molecular consequence:

NM_001113525.2:c.*899C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152287.4:c.*899C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000135.4:c.4155G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286167.3:c.4155G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_110122.2:n.2899C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110126.2:n.2782C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110128.2:n.2722C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110129.2:n.2816C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Taxonomy Links for Protein (Select 691211252) (1)
Taxonomy
Bacillus paranthracis strain EFR-4 chromosome
Bacillus paranthracis strain EFR-4 chromosome
gi|1929974118|gnl|Prokka|SAMN164956 N16494341assembly_1_3|gb|CP064079.1|

Nucleotide
TRUB1 TruB pseudouridine synthase family member 1 [Homo sapiens]
TRUB1 TruB pseudouridine synthase family member 1 [Homo sapiens]
Gene ID:142940

Gene
Gene Links for GEO Profiles (Select 42563596) (1)
Gene
Gene Links for GEO Profiles (Select 42578855) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001225502	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 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

SCV001225502

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 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, SCV001225502.5

#	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 (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1385 of the FANCA protein (p.Glu1385Asp). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. 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. 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 not expected to disrupt FANCA protein function. ClinVar contains an entry for this variant (Variation ID: 855510).

#	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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