6-32847198-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000593.6(TAP1):c.1910A>G(p.Asp637Gly) variant causes a missense change. The variant allele was found at a frequency of 0.149 in 1,611,520 control chromosomes in the GnomAD database, including 18,910 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. D637D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.17 ( 2418 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16492 hom. )

Consequence

TAP1
NM_000593.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.48

Publications

96 publications found

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 Gene-Disease associations (from GenCC):

proteasome-associated autoinflammatory syndrome 3
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

PSMB9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020890832).

BP6

Variant 6-32847198-T-C is Benign according to our data. Variant chr6-32847198-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 13730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP1	NM_000593.6 link	c.1910A>G	p.Asp637Gly	missense_variant	Exon 10 of 11	ENST00000354258.5	NP_000584.3
TAP1	NM_001292022.2 link	c.1307A>G	p.Asp436Gly	missense_variant	Exon 10 of 11		NP_001278951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5 link	c.1910A>G	p.Asp637Gly	missense_variant	Exon 10 of 11	1	NM_000593.6	ENSP00000346206.5

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26544

AN:

152066

Hom.:

2401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.156

GnomAD2 exomes

AF:

0.170

AC:

41650

AN:

244650

AF XY:

0.168

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.186

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.147

AC:

213920

AN:

1459336

Hom.:

16492

Cov.:

AF XY:

0.149

AC XY:

107911

AN XY:

726094

show subpopulations

African (AFR)

AF:

0.237

AC:

7947

AN:

33474

American (AMR)

AF:

0.181

AC:

8107

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

4110

AN:

26132

East Asian (EAS)

AF:

0.135

AC:

5351

AN:

39698

South Asian (SAS)

AF:

0.218

AC:

18782

AN:

86258

European-Finnish (FIN)

AF:

0.178

AC:

9056

AN:

50972

Middle Eastern (MID)

AF:

0.192

AC:

1105

AN:

5768

European-Non Finnish (NFE)

AF:

0.135

AC:

150233

AN:

1111948

Other (OTH)

AF:

0.153

AC:

9229

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12215

24430

36646

48861

61076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5462

10924

16386

21848

27310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.175

AC:

26615

AN:

152184

Hom.:

2418

Cov.:

AF XY:

0.175

AC XY:

13049

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.232

AC:

9637

AN:

41504

American (AMR)

AF:

0.150

AC:

2289

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

573

AN:

3466

East Asian (EAS)

AF:

0.156

AC:

805

AN:

5176

South Asian (SAS)

AF:

0.205

AC:

989

AN:

4822

European-Finnish (FIN)

AF:

0.177

AC:

1875

AN:

10602

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.146

AC:

9895

AN:

67994

Other (OTH)

AF:

0.159

AC:

336

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1121

2242

3363

4484

5605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.155

Hom.:

4903

Bravo

AF:

0.175

TwinsUK

AF:

0.138

AC:

511

ALSPAC

AF:

0.133

AC:

514

ESP6500AA

AF:

0.223

AC:

672

ESP6500EA

AF:

0.141

AC:

762

ExAC

AF:

0.171

AC:

20419

Asia WGS

AF:

0.197

AC:

685

AN:

3478

EpiCase

AF:

0.138

EpiControl

AF:

0.137

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 18, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

May 01, 1992

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.64

.;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

N;.

PhyloP100

5.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

5.8

N;.

REVEL

Uncertain

0.30

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;.

Vest4

0.095

MPC

0.73

ClinPred

0.012

GERP RS

5.4

Varity_R

0.12

gMVP

0.61

Mutation Taster

=90/10

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over