chr6-32848699-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000593.6(TAP1):c.1519G>A(p.Asp507Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000593.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251496Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135922
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461864Hom.: 0 Cov.: 34 AF XY: 0.0000344 AC XY: 25AN XY: 727230
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74454
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1699G>A (p.D567N) alteration is located in exon 7 (coding exon 7) of the TAP1 gene. This alteration results from a G to A substitution at nucleotide position 1699, causing the aspartic acid (D) at amino acid position 567 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
MHC class I deficiency Uncertain:1
This sequence change replaces aspartic acid with asparagine at codon 567 of the TAP1 protein (p.Asp567Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs200865723, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with TAP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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