6-32847165-C-T

Position:

chr6-32847165-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000593.6(TAP1):c.1943G>A(p.Arg648Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,612,612 control chromosomes in the GnomAD database, including 1,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.057 ( 481 hom., cov: 32)

Exomes 𝑓: 0.026 ( 1055 hom. )

Consequence

TAP1
NM_000593.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.791

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004969448).

BP6

Variant 6-32847165-C-T is Benign according to our data. Variant chr6-32847165-C-T is described in ClinVar as [Benign]. Clinvar id is 466383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32847165-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 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.1943G>A	p.Arg648Gln	missense_variant	10/11	ENST00000354258.5
TAP1	NM_001292022.2 linkuse as main transcript	c.1340G>A	p.Arg447Gln	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP1	ENST00000354258.5 linkuse as main transcript	c.1943G>A	p.Arg648Gln	missense_variant	10/11	1	NM_000593.6	P1	Q03518-1

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8598

AN:

152150

Hom.:

471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0538

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0223

Gnomad OTH

AF:

0.0608

GnomAD3 exomes

AF:

0.0309

AC:

7588

AN:

245630

Hom.:

291

AF XY:

0.0270

AC XY:

3612

AN XY:

133964

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.0444

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.00382

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0411

GnomAD4 exome

AF:

0.0256

AC:

37443

AN:

1460344

Hom.:

1055

Cov.:

AF XY:

0.0246

AC XY:

17842

AN XY:

726528

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0463

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.00431

Gnomad4 FIN exome

AF:

0.00231

Gnomad4 NFE exome

AF:

0.0217

Gnomad4 OTH exome

AF:

0.0412

GnomAD4 genome

AF:

0.0567

AC:

8639

AN:

152268

Hom.:

481

Cov.:

AF XY:

0.0542

AC XY:

4039

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.0537

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.0222

Gnomad4 OTH

AF:

0.0601

Alfa

AF:

0.0357

Hom.:

235

Bravo

AF:

0.0648

TwinsUK

AF:

0.0178

AC:

ALSPAC

AF:

0.0213

AC:

ESP6500AA

AF:

0.123

AC:

373

ESP6500EA

AF:

0.0292

AC:

158

ExAC

AF:

0.0301

AC:

3593

Asia WGS

AF:

0.0180

AC:

AN:

3478

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

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.79

.;T

MetaRNN

Benign

0.0050

T;T

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.2e-15

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

N;.

REVEL

Uncertain

0.55

Sift

Uncertain

0.0080

D;.

Sift4G

Uncertain

0.010

D;.

Polyphen

1.0

D;.

Vest4

0.15

MPC

1.6

ClinPred

0.036

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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