rs148154682
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000135.4(FANCA):c.1682C>T(p.Thr561Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000489 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T561R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000135.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.1682C>T | p.Thr561Met | missense_variant | 18/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.1682C>T | p.Thr561Met | missense_variant | 18/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.1682C>T | p.Thr561Met | missense_variant | 18/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000916 AC: 23AN: 251122Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135772
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461706Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 34AN XY: 727146
GnomAD4 genome AF: 0.000105 AC: 16AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74346
ClinVar
Submissions by phenotype
Fanconi anemia complementation group A Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 31, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jun 01, 2017 | - - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 09, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 561 of the FANCA protein (p.Thr561Met). This variant is present in population databases (rs148154682, gnomAD 0.06%). This missense change has been observed in individual(s) with breast cancer (PMID: 23021409). ClinVar contains an entry for this variant (Variation ID: 552283). 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 expected to disrupt FANCA 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at