rs41551515

Positions:

chr6-32847125-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000593.6(TAP1):c.1983G>A(p.Pro661Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 1,612,922 control chromosomes in the GnomAD database, including 792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 68 hom., cov: 32)

Exomes 𝑓: 0.029 ( 724 hom. )

Consequence

TAP1
NM_000593.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.681

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:

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:

TAP1 (HGNC:):

TAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 6-32847125-C-T is Benign according to our data. Variant chr6-32847125-C-T is described in ClinVar as [Benign]. Clinvar id is 466384.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32847125-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.681 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0283 (4310/152312) while in subpopulation SAS AF= 0.034 (164/4826). AF 95% confidence interval is 0.0312. There are 68 homozygotes in gnomad4. There are 2124 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 68 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP1	NM_000593.6 linkuse as main transcript	c.1983G>A	p.Pro661Pro	synonymous_variant	10/11	ENST00000354258.5	NP_000584.3	Q03518-1A0A0S2Z5A6X5CKB3
TAP1	NM_001292022.2 linkuse as main transcript	c.1380G>A	p.Pro460Pro	synonymous_variant	10/11		NP_001278951.1	Q03518B7Z7P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5 linkuse as main transcript	c.1983G>A	p.Pro661Pro	synonymous_variant	10/11	1	NM_000593.6	ENSP00000346206.5		Q03518-1

Frequencies

GnomAD3 genomes

AF:

0.0283

AC:

4307

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0287

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0335

Gnomad FIN

AF:

0.0359

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0162

GnomAD3 exomes

AF:

0.0277

AC:

6822

AN:

246340

Hom.:

151

AF XY:

0.0284

AC XY:

3818

AN XY:

134302

show subpopulations

Gnomad AFR exome

AF:

0.0291

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.00963

Gnomad EAS exome

AF:

0.000602

Gnomad SAS exome

AF:

0.0378

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0340

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0291

AC:

42509

AN:

1460610

Hom.:

724

Cov.:

AF XY:

0.0295

AC XY:

21440

AN XY:

726620

show subpopulations

Gnomad4 AFR exome

AF:

0.0308

Gnomad4 AMR exome

AF:

0.0138

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.0374

Gnomad4 FIN exome

AF:

0.0341

Gnomad4 NFE exome

AF:

0.0306

Gnomad4 OTH exome

AF:

0.0255

GnomAD4 genome

AF:

0.0283

AC:

4310

AN:

152312

Hom.:

Cov.:

AF XY:

0.0285

AC XY:

2124

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0286

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0340

Gnomad4 FIN

AF:

0.0359

Gnomad4 NFE

AF:

0.0323

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0297

Hom.:

Bravo

AF:

0.0262

Asia WGS

AF:

0.0290

AC:

103

AN:

3478

EpiCase

AF:

0.0303

EpiControl

AF:

0.0290

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over