NM_000135.4(FANCA):c.4190C>A (p.Thr1397Lys) AND Fanconi anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 4, 2023
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:: RCV003522385.2

Allele description [Variation Report for NM_000135.4(FANCA):c.4190C>A (p.Thr1397Lys)]

NM_000135.4(FANCA):c.4190C>A (p.Thr1397Lys)

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.4190C>A (p.Thr1397Lys)

HGVS:

NC_000016.10:g.89738952G>T
NG_011706.1:g.82706C>A
NM_000135.4:c.4190C>AMANE SELECT
NM_001113525.2:c.*706G>TMANE SELECT
NM_001286167.3:c.4194C>A
NM_152287.4:c.*706G>T
NP_000126.2:p.Thr1397Lys
NP_000126.2:p.Thr1397Lys
NP_001273096.1:p.Asn1398Lys
LRG_495t1:c.4190C>A
LRG_495:g.82706C>A
LRG_495p1:p.Thr1397Lys
NC_000016.9:g.89805360G>T
NM_000135.2:c.4190C>A
NR_110122.2:n.2706G>T
NR_110126.2:n.2589G>T
NR_110128.2:n.2529G>T
NR_110129.2:n.2623G>T

Protein change:

N1398K

Molecular consequence:

NM_001113525.2:c.*706G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152287.4:c.*706G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000135.4:c.4190C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001286167.3:c.4194C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_110122.2:n.2706G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110126.2:n.2589G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110128.2:n.2529G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110129.2:n.2623G>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004276892	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 4, 2023)	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

SCV004276892

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 4, 2023)

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, SCV004276892.1

#	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 threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 1397 of the FANCA protein (p.Thr1397Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FANCA protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

ClinVar

Relating variation to medicine