NM_000593.6:c.1957T>A
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_000593.6(TAP1):c.1957T>A(p.Leu653Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000593.6 missense
Scores
Clinical Significance
Conservation
Publications
- proteasome-associated autoinflammatory syndrome 3Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000122 AC: 3AN: 246064 AF XY: 0.0000224 show subpopulations
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460566Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 726612 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74364 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
MHC class I deficiency Uncertain:1
This sequence change replaces leucine with methionine at codon 713 of the TAP1 protein (p.Leu713Met). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and methionine. This variant is present in population databases (rs772090667, ExAC 0.03%). 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. -
Inborn genetic diseases Uncertain:1
The c.2137T>A (p.L713M) alteration is located in exon 10 (coding exon 10) of the TAP1 gene. This alteration results from a T to A substitution at nucleotide position 2137, causing the leucine (L) at amino acid position 713 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at