dbSNP rs145837211: TAPBP:p.Trp487Cys (chr6-33303829-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_172208.3(TAPBP):c.1461G>C(p.Trp487Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,595,790 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 10 hom. )

Consequence

TAPBP
NM_172208.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0610

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003785193).

BP6

Variant 6-33303829-C-G is Benign according to our data. Variant chr6-33303829-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3770557.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-33303829-C-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAPBP	NM_003190.5 link	c.1335+126G>C		intron_variant	Intron 7 of 7	ENST00000434618.7	NP_003181.3	O15533-1A0A024RCT1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7 link	c.1335+126G>C		intron_variant	Intron 7 of 7	1	NM_003190.5	ENSP00000395701.2		O15533-1

Frequencies

GnomAD3 genomes

AF:

0.00196

AC:

298

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00248

AC:

546

AN:

220550

Hom.:

AF XY:

0.00271

AC XY:

322

AN XY:

118932

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.00485

Gnomad EAS exome

AF:

0.00189

Gnomad SAS exome

AF:

0.00782

Gnomad FIN exome

AF:

0.000872

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00250

GnomAD4 exome

AF:

0.00162

AC:

2335

AN:

1443652

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

1299

AN XY:

716556

show subpopulations

Gnomad4 AFR exome

AF:

0.00310

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00509

Gnomad4 EAS exome

AF:

0.00137

Gnomad4 SAS exome

AF:

0.00766

Gnomad4 FIN exome

AF:

0.00104

Gnomad4 NFE exome

AF:

0.000935

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00195

AC:

297

AN:

152138

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00252

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00206

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00220

AC:

ExAC

AF:

0.00208

AC:

252

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TAPBP: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.6

DANN

Benign

0.94

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.23

REVEL

Benign

0.026

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.18

MutPred

0.58

Gain of sheet (P = 0.039);

MVP

0.099

MPC

1.4

ClinPred

0.068

GERP RS

0.85

gMVP

0.28

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

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