rs144706539

Variant names:

• chr6-33304176-G-A
• rs144706539
• NM_003190.5:c.1252C>T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.98

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]

ACMG classification

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 rank	MANE	Protein	UniProt
TAPBP	NM_003190.5	c.1252C>T	p.Leu418Leu	synonymous_variant	Exon 6 of 8	ENST00000434618.7	NP_003181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7	c.1252C>T	p.Leu418Leu	synonymous_variant	Exon 6 of 8	1	NM_003190.5	ENSP00000395701.2

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1922 AN: 151732 Hom.: 19 Cov.: 31

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.: 34 AF XY: 0.0129 AC XY: 1749 AN XY: 135742

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.: 32 AF XY: 0.0163 AC XY: 11862 AN XY: 727202

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.: 19 Cov.: 31 AF XY: 0.0119 AC XY: 882 AN XY: 74208

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.: 15

Bravo AF: 0.0145

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.0201

EpiControl AF: 0.0218

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

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

- -

TAPBP-related disorder Benign:1

Jul 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Other links and lift over

dbSNP: rs144706539; hg19: chr6-33271953; COSMIC: COSV70457436; COSMIC: COSV70457436;