rs192572056
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000593.6(TAP1):c.1601C>T(p.Thr534Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,612,430 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T534T) has been classified as Likely benign.
Frequency
Consequence
NM_000593.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAP1 | NM_000593.6 | c.1601C>T | p.Thr534Met | missense_variant | 8/11 | ENST00000354258.5 | |
TAP1 | NM_001292022.2 | c.998C>T | p.Thr333Met | missense_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAP1 | ENST00000354258.5 | c.1601C>T | p.Thr534Met | missense_variant | 8/11 | 1 | NM_000593.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000492 AC: 12AN: 243986Hom.: 1 AF XY: 0.0000601 AC XY: 8AN XY: 133182
GnomAD4 exome AF: 0.0000336 AC: 49AN: 1460072Hom.: 2 Cov.: 32 AF XY: 0.0000303 AC XY: 22AN XY: 726360
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74512
ClinVar
Submissions by phenotype
MHC class I deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 594 of the TAP1 protein (p.Thr594Met). This variant is present in population databases (rs192572056, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 582193). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The methionine 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