rs1057149

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

32 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 -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 VariationId is 466383.Status of the report is criteria_provided_single_submitter, 1 stars.

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 rank	MANE	Protein	UniProt
TAP1	NM_000593.6 link	c.1943G>A	p.Arg648Gln	missense_variant	Exon 10 of 11	ENST00000354258.5	NP_000584.3	Q03518-1A0A0S2Z5A6X5CKB3
TAP1	NM_001292022.2 link	c.1340G>A	p.Arg447Gln	missense_variant	Exon 10 of 11		NP_001278951.1	Q03518B7Z7P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5 link	c.1943G>A	p.Arg648Gln	missense_variant	Exon 10 of 11	1	NM_000593.6	ENSP00000346206.5		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

GnomAD2 exomes

AF:

0.0309

AC:

7588

AN:

245630

AF XY:

0.0270

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 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

African (AFR)

AF:

0.139

AC:

4656

AN:

33476

American (AMR)

AF:

0.0463

AC:

2071

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

3271

AN:

26136

East Asian (EAS)

AF:

0.000680

AC:

AN:

39700

South Asian (SAS)

AF:

0.00431

AC:

372

AN:

86258

European-Finnish (FIN)

AF:

0.00231

AC:

120

AN:

51898

Middle Eastern (MID)

AF:

0.0596

AC:

344

AN:

5768

European-Non Finnish (NFE)

AF:

0.0217

AC:

24097

AN:

1112004

Other (OTH)

AF:

0.0412

AC:

2485

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2306

4612

6917

9223

11529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1016

2032

3048

4064

5080

<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:

0.0567

AC:

8639

AN:

152268

Hom.:

481

Cov.:

AF XY:

0.0542

AC XY:

4039

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.137

AC:

5670

AN:

41524

American (AMR)

AF:

0.0537

AC:

822

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

452

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5182

South Asian (SAS)

AF:

0.00456

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0222

AC:

1513

AN:

68016

Other (OTH)

AF:

0.0601

AC:

127

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

392

784

1176

1568

1960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0363

Hom.:

709

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.

PhyloP100

0.79

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

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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