6-32850997-T-C

Position:

chr6-32850997-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000354258.5(TAP1):c.997A>G(p.Ile333Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,592 control chromosomes in the GnomAD database, including 26,484 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3250 hom., cov: 31)

Exomes 𝑓: 0.17 ( 23234 hom. )

Consequence

TAP1
ENST00000354258.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.18

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029444993).

BP6

Variant 6-32850997-T-C is Benign according to our data. Variant chr6-32850997-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 13729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32850997-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP1	NM_000593.6 linkuse as main transcript	c.997A>G	p.Ile333Val	missense_variant	4/11	ENST00000354258.5	NP_000584.3
TAP1	NM_001292022.2 linkuse as main transcript	c.394A>G	p.Ile132Val	missense_variant	4/11		NP_001278951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5 linkuse as main transcript	c.997A>G	p.Ile333Val	missense_variant	4/11	1	NM_000593.6	ENSP00000346206	P1	Q03518-1

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30547

AN:

151824

Hom.:

3227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.176

GnomAD3 exomes

AF:

0.200

AC:

49398

AN:

246808

Hom.:

5284

AF XY:

0.200

AC XY:

26887

AN XY:

134488

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.186

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.229

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.174

AC:

253703

AN:

1460652

Hom.:

23234

Cov.:

AF XY:

0.177

AC XY:

128309

AN XY:

726626

show subpopulations

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.202

AC:

30628

AN:

151940

Hom.:

3250

Cov.:

AF XY:

0.203

AC XY:

15111

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.177

Hom.:

4380

Bravo

AF:

0.200

TwinsUK

AF:

0.163

AC:

604

ALSPAC

AF:

0.157

AC:

604

ESP6500AA

AF:

0.253

AC:

764

ESP6500EA

AF:

0.165

AC:

891

ExAC

AF:

0.203

AC:

23981

Asia WGS

AF:

0.268

AC:

931

AN:

3478

EpiCase

AF:

0.160

EpiControl

AF:

0.159

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jan 18, 2022	- -

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.3

DANN

Benign

0.73

DEOGEN2

Benign

0.12

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.027

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.37

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.22

REVEL

Benign

0.16

Sift

Benign

0.68

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.0050

MPC

0.46

ClinPred

0.00087

GERP RS

-2.4

Varity_R

0.029

gMVP

0.58

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