Variant rs1057373 details in Genebe, Genetics Data Aggregator

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

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]

TAP1 links:

PSMB8-AS1 (HGNC:39758): (PSMB8 antisense RNA 1 (head to head))

PSMB8-AS1 links:

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]

PSMB9 links:

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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
TAP1	NM_000593.6 linkuse as main transcript	c.*77G>T		3_prime_UTR_variant	11/11	ENST00000354258.5
PSMB8-AS1	NR_037173.1 linkuse as main transcript	n.500C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP1	ENST00000354258.5 linkuse as main transcript	c.*77G>T		3_prime_UTR_variant	11/11	1	NM_000593.6	P1	Q03518-1
PSMB8-AS1	ENST00000453426.2 linkuse as main transcript	n.274C>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0821

AC:

12494

AN:

152096

Hom.:

577

Cov.:

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.:

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.:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over