rs747106102
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003190.5(TAPBP):āc.464C>Gā(p.Ala155Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,605,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000032 ( 0 hom. )
Consequence
TAPBP
NM_003190.5 missense
NM_003190.5 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 2.87
Genes affected
TAPBP (HGNC:11566): (TAP binding protein) This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.29088646).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAPBP | NM_003190.5 | c.464C>G | p.Ala155Gly | missense_variant | 3/8 | ENST00000434618.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAPBP | ENST00000434618.7 | c.464C>G | p.Ala155Gly | missense_variant | 3/8 | 1 | NM_003190.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000808 AC: 2AN: 247580Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134018
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GnomAD4 exome AF: 0.0000323 AC: 47AN: 1452962Hom.: 0 Cov.: 32 AF XY: 0.0000264 AC XY: 19AN XY: 720952
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MHC class I deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 04, 2023 | ClinVar contains an entry for this variant (Variation ID: 466398). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 155 of the TAPBP protein (p.Ala155Gly). This variant is present in population databases (rs747106102, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TAPBP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
D;D;D;D
Sift4G
Pathogenic
D;D;D;.
Polyphen
1.0
.;D;.;.
Vest4
MVP
MPC
0.36
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at