rs59328013
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000593.6(TAP1):c.739G>T(p.Gly247Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G247E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000593.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAP1 | NM_000593.6 | c.739G>T | p.Gly247Trp | missense_variant | 3/11 | ENST00000354258.5 | |
TAP1 | NM_001292022.2 | c.136G>T | p.Gly46Trp | missense_variant | 3/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAP1 | ENST00000354258.5 | c.739G>T | p.Gly247Trp | missense_variant | 3/11 | 1 | NM_000593.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152046Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000203 AC: 5AN: 246710Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134440
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1460774Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 726700
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74290
ClinVar
Submissions by phenotype
MHC class I deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 21, 2021 | This sequence change replaces glycine with tryptophan at codon 307 of the TAP1 protein (p.Gly307Trp). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and tryptophan. This variant is present in population databases (rs59328013, ExAC 0.02%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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