rs199938598
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBS1_Supporting
The NM_000135.4(FANCA):c.2210C>T(p.Ala737Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000702 in 1,610,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. 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. A737T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000135.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.2210C>T | p.Ala737Val | missense_variant | 24/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.2210C>T | p.Ala737Val | missense_variant | 24/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.2210C>T | p.Ala737Val | missense_variant | 24/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152154Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000165 AC: 4AN: 242752Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131668
GnomAD4 exome AF: 0.0000727 AC: 106AN: 1458362Hom.: 1 Cov.: 32 AF XY: 0.0000621 AC XY: 45AN XY: 725130
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152272Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5AN XY: 74454
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2023 | 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: 456093). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. This variant is present in population databases (rs199938598, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 737 of the FANCA protein (p.Ala737Val). - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Fanconi anemia complementation group A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 22, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at