chr6-32847198-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000593.6(TAP1):āc.1910A>Gā(p.Asp637Gly) variant causes a missense change. The variant allele was found at a frequency of 0.149 in 1,611,520 control chromosomes in the GnomAD database, including 18,910 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.17 ( 2418 hom., cov: 32)
Exomes š: 0.15 ( 16492 hom. )
Consequence
TAP1
NM_000593.6 missense
NM_000593.6 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 5.48
Genes affected
TAP1 (HGNC:43): (transporter 1, ATP binding cassette subfamily B member) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]
PSMB9 (HGNC:9546): (proteasome 20S subunit beta 9) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0020890832).
BP6
Variant 6-32847198-T-C is Benign according to our data. Variant chr6-32847198-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 13730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32847198-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TAP1 | NM_000593.6 | c.1910A>G | p.Asp637Gly | missense_variant | 10/11 | ENST00000354258.5 | NP_000584.3 | |
TAP1 | NM_001292022.2 | c.1307A>G | p.Asp436Gly | missense_variant | 10/11 | NP_001278951.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TAP1 | ENST00000354258.5 | c.1910A>G | p.Asp637Gly | missense_variant | 10/11 | 1 | NM_000593.6 | ENSP00000346206.5 |
Frequencies
GnomAD3 genomes AF: 0.175 AC: 26544AN: 152066Hom.: 2401 Cov.: 32
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GnomAD3 exomes AF: 0.170 AC: 41650AN: 244650Hom.: 3749 AF XY: 0.168 AC XY: 22478AN XY: 133578
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GnomAD4 exome AF: 0.147 AC: 213920AN: 1459336Hom.: 16492 Cov.: 33 AF XY: 0.149 AC XY: 107911AN XY: 726094
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GnomAD4 genome AF: 0.175 AC: 26615AN: 152184Hom.: 2418 Cov.: 32 AF XY: 0.175 AC XY: 13049AN XY: 74400
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MHC class I deficiency Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 18, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
PEPTIDE TRANSPORTER PSF1 POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | May 01, 1992 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
P;P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
T;.
Sift4G
Benign
T;.
Polyphen
B;.
Vest4
MPC
ClinPred
T
GERP RS
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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