rs41561219

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000593.6(TAP1):c.1552G>A(p.Val518Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 1,613,974 control chromosomes in the GnomAD database, including 785 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 Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 64 hom., cov: 32)

Exomes 𝑓: 0.029 ( 721 hom. )

Consequence

TAP1
NM_000593.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.462

Publications

13 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=0.0020525157).

BP6

Variant 6-32848666-C-T is Benign according to our data. Variant chr6-32848666-C-T is described in ClinVar as Benign. ClinVar VariationId is 466382.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0281 (4280/152216) while in subpopulation SAS AF = 0.0342 (165/4820). AF 95% confidence interval is 0.0311. There are 64 homozygotes in GnomAd4. There are 2105 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP1	NM_000593.6 link	c.1552G>A	p.Val518Ile	missense_variant	Exon 7 of 11	ENST00000354258.5	NP_000584.3	Q03518-1A0A0S2Z5A6X5CKB3
TAP1	NM_001292022.2 link	c.949G>A	p.Val317Ile	missense_variant	Exon 7 of 11		NP_001278951.1	Q03518B7Z7P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5 link	c.1552G>A	p.Val518Ile	missense_variant	Exon 7 of 11	1	NM_000593.6	ENSP00000346206.5		Q03518-1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4277

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0283

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.0355

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0322

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.0276

AC:

6950

AN:

251492

AF XY:

0.0284

show subpopulations

Gnomad AFR exome

AF:

0.0277

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.00962

Gnomad EAS exome

AF:

0.000652

Gnomad FIN exome

AF:

0.0356

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0241

GnomAD4 exome

AF:

0.0290

AC:

42462

AN:

1461758

Hom.:

721

Cov.:

AF XY:

0.0295

AC XY:

21424

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.0301

AC:

1006

AN:

33474

American (AMR)

AF:

0.0133

AC:

597

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0108

AC:

281

AN:

26136

East Asian (EAS)

AF:

0.000529

AC:

AN:

39700

South Asian (SAS)

AF:

0.0375

AC:

3236

AN:

86252

European-Finnish (FIN)

AF:

0.0341

AC:

1819

AN:

53420

Middle Eastern (MID)

AF:

0.00632

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0305

AC:

33924

AN:

1111968

Other (OTH)

AF:

0.0255

AC:

1542

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

2617

5234

7851

10468

13085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1234

2468

3702

4936

6170

<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:

0.0281

AC:

4280

AN:

152216

Hom.:

Cov.:

AF XY:

0.0283

AC XY:

2105

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0282

AC:

1171

AN:

41526

American (AMR)

AF:

0.0148

AC:

226

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0342

AC:

165

AN:

4820

European-Finnish (FIN)

AF:

0.0355

AC:

376

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0322

AC:

2193

AN:

68008

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

212

424

636

848

1060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0299

Hom.:

240

Bravo

AF:

0.0259

TwinsUK

AF:

0.0326

AC:

121

ALSPAC

AF:

0.0265

AC:

102

ESP6500AA

AF:

0.0268

AC:

118

ESP6500EA

AF:

0.0285

AC:

245

ExAC

AF:

0.0297

AC:

3609

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0290

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

0.085

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.028

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.4

PhyloP100

0.46

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.56

REVEL

Benign

0.11

Sift

Benign

0.47

Sift4G

Benign

0.20

Polyphen

0.13

Vest4

0.014

MPC

0.47

ClinPred

0.00091

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.27

Mutation Taster

=99/1

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

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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