NM_000593.6:c.997A>G

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.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. 16/21 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
NM_000593.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.18

Publications

69 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=0.0029444993).

BP6

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

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 rank	MANE	Protein	UniProt
TAP1	NM_000593.6 link	c.997A>G	p.Ile333Val	missense_variant	Exon 4 of 11	ENST00000354258.5	NP_000584.3	Q03518-1A0A0S2Z5A6X5CKB3
TAP1	NM_001292022.2 link	c.394A>G	p.Ile132Val	missense_variant	Exon 4 of 11		NP_001278951.1	Q03518B7Z7P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5 link	c.997A>G	p.Ile333Val	missense_variant	Exon 4 of 11	1	NM_000593.6	ENSP00000346206.5		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

GnomAD2 exomes

AF:

0.200

AC:

49398

AN:

246808

AF XY:

0.200

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 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

African (AFR)

AF:

0.266

AC:

8888

AN:

33476

American (AMR)

AF:

0.183

AC:

8185

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5199

AN:

26136

East Asian (EAS)

AF:

0.171

AC:

6784

AN:

39696

South Asian (SAS)

AF:

0.276

AC:

23794

AN:

86258

European-Finnish (FIN)

AF:

0.207

AC:

10853

AN:

52318

Middle Eastern (MID)

AF:

0.221

AC:

1272

AN:

5750

European-Non Finnish (NFE)

AF:

0.160

AC:

177728

AN:

1111914

Other (OTH)

AF:

0.182

AC:

11000

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

13103

26206

39308

52411

65514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6420

12840

19260

25680

32100

<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:

0.202

AC:

30628

AN:

151940

Hom.:

3250

Cov.:

AF XY:

0.203

AC XY:

15111

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.261

AC:

10800

AN:

41412

American (AMR)

AF:

0.161

AC:

2460

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

718

AN:

3466

East Asian (EAS)

AF:

0.217

AC:

1117

AN:

5154

South Asian (SAS)

AF:

0.269

AC:

1293

AN:

4812

European-Finnish (FIN)

AF:

0.201

AC:

2120

AN:

10560

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11516

AN:

67950

Other (OTH)

AF:

0.178

AC:

375

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1228

2457

3685

4914

6142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.181

Hom.:

6420

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

Jan 18, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely 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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

0.064

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.3

(source)

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

PhyloP100

-1.2

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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