Variant rs144706539 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003190.5(TAPBP):c.1252C>T(p.Leu418Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,613,658 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 19 hom., cov: 31)

Exomes 𝑓: 0.016 ( 250 hom. )

Consequence

TAPBP
NM_003190.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.98

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 6-33304176-G-A is Benign according to our data. Variant chr6-33304176-G-A is described in ClinVar as [Benign]. Clinvar id is 466397.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.98 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0127 (1923/151850) while in subpopulation AMR AF= 0.0213 (324/15226). AF 95% confidence interval is 0.0194. There are 19 homozygotes in gnomad4. There are 882 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAPBP	NM_003190.5 link	c.1252C>T	p.Leu418Leu	synonymous_variant	6/8	ENST00000434618.7	NP_003181.3	O15533-1A0A024RCT1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7 link	c.1252C>T	p.Leu418Leu	synonymous_variant	6/8	1	NM_003190.5	ENSP00000395701.2		O15533-1

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1922

AN:

151732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00421

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.00748

Gnomad FIN

AF:

0.00303

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0124

AC:

3111

AN:

251128

Hom.:

AF XY:

0.0129

AC XY:

1749

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.00945

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.00857

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.0182

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0164

AC:

23973

AN:

1461808

Hom.:

250

Cov.:

AF XY:

0.0163

AC XY:

11862

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00335

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.00918

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.00918

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.0189

Gnomad4 OTH exome

AF:

0.0149

GnomAD4 genome

AF:

0.0127

AC:

1923

AN:

151850

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

882

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.00420

Gnomad4 AMR

AF:

0.0213

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00117

Gnomad4 SAS

AF:

0.00749

Gnomad4 FIN

AF:

0.00303

Gnomad4 NFE

AF:

0.0184

Gnomad4 OTH

AF:

0.0186

Alfa

AF:

0.0166

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0201

EpiControl

AF:

0.0218

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

TAPBP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.1

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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