rs750421982
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000135.4(FANCA):c.3000C>G(p.His1000Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251410Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135896
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461614Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727132
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:2
This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1000 of the FANCA protein (p.His1000Gln). This variant is present in population databases (rs750421982, gnomAD 0.01%). This missense change has been observed in individual(s) with head and neck carcinoma (PMID: 28678401). ClinVar contains an entry for this variant (Variation ID: 456107). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FANCA protein function with a negative predictive value of 95%. 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. -
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not provided Uncertain:2
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The FANCA c.3000C>G (p.His1000Gln) variant has been reported in the published literature in an individual with head and neck cancer (PMID: 28678401 (2017)). The frequency of this variant in the general population, 0.000054 (7/129176 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. -
not specified Uncertain:1
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Fanconi anemia complementation group A Uncertain:1
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at