rs1057373

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000593.6(TAP1):​c.*77G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 1,497,186 control chromosomes in the GnomAD database, including 6,750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.082 ( 584 hom., cov: 32)
Exomes 𝑓: 0.091 ( 6166 hom. )

Consequence

TAP1
NM_000593.6 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.181
Variant links:
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]
PSMB8-AS1 (HGNC:39758): (PSMB8 antisense RNA 1 (head to head))
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TAP1NM_000593.6 linkuse as main transcriptc.*77G>T 3_prime_UTR_variant 11/11 ENST00000354258.5
PSMB8-AS1NR_037173.1 linkuse as main transcriptn.500C>A non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAP1ENST00000354258.5 linkuse as main transcriptc.*77G>T 3_prime_UTR_variant 11/111 NM_000593.6 P1Q03518-1
PSMB8-AS1ENST00000453426.2 linkuse as main transcriptn.274C>A non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.0821
AC:
12494
AN:
152096
Hom.:
577
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0434
Gnomad AMI
AF:
0.113
Gnomad AMR
AF:
0.0763
Gnomad ASJ
AF:
0.0262
Gnomad EAS
AF:
0.151
Gnomad SAS
AF:
0.150
Gnomad FIN
AF:
0.140
Gnomad MID
AF:
0.0764
Gnomad NFE
AF:
0.0907
Gnomad OTH
AF:
0.0742
GnomAD4 exome
AF:
0.0911
AC:
122579
AN:
1344972
Hom.:
6166
Cov.:
23
AF XY:
0.0932
AC XY:
62813
AN XY:
673660
show subpopulations
Gnomad4 AFR exome
AF:
0.0444
Gnomad4 AMR exome
AF:
0.119
Gnomad4 ASJ exome
AF:
0.0218
Gnomad4 EAS exome
AF:
0.133
Gnomad4 SAS exome
AF:
0.152
Gnomad4 FIN exome
AF:
0.142
Gnomad4 NFE exome
AF:
0.0841
Gnomad4 OTH exome
AF:
0.0841
GnomAD4 genome
AF:
0.0822
AC:
12519
AN:
152214
Hom.:
584
Cov.:
32
AF XY:
0.0854
AC XY:
6357
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.0432
Gnomad4 AMR
AF:
0.0774
Gnomad4 ASJ
AF:
0.0262
Gnomad4 EAS
AF:
0.152
Gnomad4 SAS
AF:
0.150
Gnomad4 FIN
AF:
0.140
Gnomad4 NFE
AF:
0.0907
Gnomad4 OTH
AF:
0.0781
Alfa
AF:
0.0886
Hom.:
1272
Bravo
AF:
0.0761
Asia WGS
AF:
0.132
AC:
457
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
9.9
DANN
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1057373; hg19: chr6-32813279; COSMIC: COSV62754256; COSMIC: COSV62754256; API