rs2071888

Positions:

chr6-33305078-G-C

Variant summary

Our verdict is Benign. Variant got -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. 13/18 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 403518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-33305078-G-C is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAPBP	NM_003190.5 linkuse as main transcript	c.779C>G	p.Thr260Arg	missense_variant	4/8	ENST00000434618.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAPBP	ENST00000434618.7 linkuse as main transcript	c.779C>G	p.Thr260Arg	missense_variant	4/8	1	NM_003190.5	P2	O15533-1

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

GnomAD3 exomes

AF:

0.559

AC:

140530

AN:

251460

Hom.:

40181

AF XY:

0.563

AC XY:

76453

AN XY:

135904

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 SAS exome

AF:

0.655

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

Gnomad4 AFR exome

AF:

0.746

Gnomad4 AMR exome

AF:

0.547

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.375

Gnomad4 SAS exome

AF:

0.654

Gnomad4 FIN exome

AF:

0.529

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.558

GnomAD4 genome

AF:

0.593

AC:

90140

AN:

152000

Hom.:

27444

Cov.:

AF XY:

0.593

AC XY:

44066

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.736

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.577

Gnomad4 EAS

AF:

0.406

Gnomad4 SAS

AF:

0.650

Gnomad4 FIN

AF:

0.527

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.583

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

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.18

DEOGEN2

Benign

0.0040

.;T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.027

T;T;T;T

MetaRNN

Benign

0.0000046

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.040

N;N;N;N

REVEL

Benign

0.064

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0

.;B;.;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over