6-33305078-G-C

Variant names:

Variant summary

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

The NM_003190.5(TAPBP):c.779C>G(p.Thr260Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,613,886 control chromosomes in the GnomAD database, including 241,705 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T260G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.59 ( 27444 hom., cov: 31)

Exomes 𝑓: 0.54 ( 214261 hom. )

Consequence

TAPBP
NM_003190.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.365

Publications

59 publications found

Variant links:

Genes affected

TAPBP (HGNC:11566): (TAP binding protein) This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

TAPBP Gene-Disease associations (from GenCC):

MHC class I deficiency
Inheritance: AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

TAPBP 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=4.641656E-6).

BP6

Variant 6-33305078-G-C is Benign according to our data. Variant chr6-33305078-G-C is described in ClinVar as Benign. ClinVar VariationId is 403518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003190.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TAPBP	NM_003190.5	MANE Select	c.779C>G	p.Thr260Arg	missense	Exon 4 of 8	NP_003181.3
TAPBP	NM_172208.3		c.779C>G	p.Thr260Arg	missense	Exon 4 of 7	NP_757345.2
TAPBP	NM_001410875.1		c.779C>G	p.Thr260Arg	missense	Exon 4 of 7	NP_001397804.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TAPBP	ENST00000434618.7	TSL:1 MANE Select	c.779C>G	p.Thr260Arg	missense	Exon 4 of 8	ENSP00000395701.2
TAPBP	ENST00000426633.6	TSL:1	c.779C>G	p.Thr260Arg	missense	Exon 4 of 7	ENSP00000404833.2
TAPBP	ENST00000489157.6	TSL:1	c.518C>G	p.Thr173Arg	missense	Exon 3 of 7	ENSP00000419659.1

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90039

AN:

151882

Hom.:

27396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.735

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.527

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.585

GnomAD2 exomes

AF:

0.559

AC:

140530

AN:

251460

AF XY:

0.563

show subpopulations

Gnomad AFR exome

AF:

0.749

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.567

Gnomad EAS exome

AF:

0.379

Gnomad FIN exome

AF:

0.527

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.567

GnomAD4 exome

AF:

0.538

AC:

786499

AN:

1461886

Hom.:

214261

Cov.:

AF XY:

0.542

AC XY:

394195

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.746

AC:

24963

AN:

33480

American (AMR)

AF:

0.547

AC:

24474

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

14924

AN:

26136

East Asian (EAS)

AF:

0.375

AC:

14901

AN:

39700

South Asian (SAS)

AF:

0.654

AC:

56371

AN:

86258

European-Finnish (FIN)

AF:

0.529

AC:

28234

AN:

53420

Middle Eastern (MID)

AF:

0.579

AC:

3341

AN:

5768

European-Non Finnish (NFE)

AF:

0.527

AC:

585603

AN:

1112008

Other (OTH)

AF:

0.558

AC:

33688

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

26600

53200

79801

106401

133001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16794

33588

50382

67176

83970

<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:

0.593

AC:

90140

AN:

152000

Hom.:

27444

Cov.:

AF XY:

0.593

AC XY:

44066

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.736

AC:

30516

AN:

41464

American (AMR)

AF:

0.578

AC:

8828

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.577

AC:

2002

AN:

3468

East Asian (EAS)

AF:

0.406

AC:

2090

AN:

5146

South Asian (SAS)

AF:

0.650

AC:

3137

AN:

4824

European-Finnish (FIN)

AF:

0.527

AC:

5566

AN:

10556

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.533

AC:

36250

AN:

67952

Other (OTH)

AF:

0.583

AC:

1228

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1819

3638

5456

7275

9094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.552

Hom.:

7526

Bravo

AF:

0.601

TwinsUK

AF:

0.518

AC:

1922

ALSPAC

AF:

0.526

AC:

2026

ESP6500AA

AF:

0.736

AC:

3241

ESP6500EA

AF:

0.542

AC:

4662

ExAC

AF:

0.568

AC:

68959

Asia WGS

AF:

0.526

AC:

1831

AN:

3478

EpiCase

AF:

0.549

EpiControl

AF:

0.543

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

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

May 28, 2019

Mendelics

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, associated with juvenile rheumatoid arthritis

not provided

Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0040

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.027

MetaRNN

Benign

0.0000046

MetaSVM

Benign

-1.0

PhyloP100

0.36

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.040

REVEL

Benign

0.064

Sift

Benign

1.0

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.069

MPC

0.39

ClinPred

0.00071

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.29

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over