NM_000135.4(FANCA):c.4196C>T (p.Ala1399Val) AND Fanconi anemia complementation group A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 29, 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:: RCV002282639.1

Allele description [Variation Report for NM_000135.4(FANCA):c.4196C>T (p.Ala1399Val)]

NM_000135.4(FANCA):c.4196C>T (p.Ala1399Val)

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.4196C>T (p.Ala1399Val)

HGVS:

NC_000016.10:g.89738946G>A
NG_011706.1:g.82712C>T
NM_000135.4:c.4196C>TMANE SELECT
NM_001113525.2:c.*700G>AMANE SELECT
NM_001286167.3:c.4200C>T
NM_152287.4:c.*700G>A
NP_000126.2:p.Ala1399Val
NP_000126.2:p.Ala1399Val
NP_001273096.1:p.Ser1400=
LRG_495t1:c.4196C>T
LRG_495:g.82712C>T
LRG_495p1:p.Ala1399Val
NC_000016.9:g.89805354G>A
NM_000135.2:c.4196C>T
NR_110122.2:n.2700G>A
NR_110126.2:n.2583G>A
NR_110128.2:n.2523G>A
NR_110129.2:n.2617G>A

Protein change:

A1399V

Links:

dbSNP: rs1457671800

NCBI 1000 Genomes Browser:

rs1457671800

Molecular consequence:

NM_001113525.2:c.*700G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152287.4:c.*700G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000135.4:c.4196C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110122.2:n.2700G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110126.2:n.2583G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110128.2:n.2523G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110129.2:n.2617G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001286167.3:c.4200C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Fanconi anemia complementation group A
Synonyms:: Fanconi anemia, group A
Identifiers:: MONDO: MONDO:0009215; MedGen: C3469521; Orphanet: 84; OMIM: 227650

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Serratia marcescens voucher RIFA 1361 16S ribosomal RNA gene, partial sequence
Serratia marcescens voucher RIFA 1361 16S ribosomal RNA gene, partial sequence
gi|699059035|gb|KF624752.1|

Nucleotide
Pandoraea sp. 2 RIFA 1481 16S ribosomal RNA gene, partial sequence
Pandoraea sp. 2 RIFA 1481 16S ribosomal RNA gene, partial sequence
gi|699059028|gb|KF624745.1|

Nucleotide
Protein Links for Nucleotide (Select 639235745) (640)
Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002570385	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 29, 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

SCV002570385

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 29, 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV002570385.1

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

Description

This FANCA missense variant (rs1457671800) is rare (<0.1%) in a large population dataset (gnomAD: 1/251486 total alleles; 0.0004%; no homozygotes). This variant has been reported in ClinVar [Variation ID 1399364], but has not been reported in the literature, to our knowledge. Of three bioinformatics tools queried, two predict that the substitution would be damaging while one predicts that it would be tolerated. The alanine residue at this position is evolutionarily conserved across most species assessed. We consider the clinical significance of c.4196C>T to be uncertain at this time.

#	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

ClinVar

Relating variation to medicine