6-33304764-A-T

Position:

• chr6-33304764-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003190.5(TAPBP):​c.869-126T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,275,234 control chromosomes in the GnomAD database, including 151,757 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (14098 hom., cov: 32)
  • Exomes 𝑓: 0.49 (137659 hom.)
• Consequence: TAPBP NM_003190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAPBP	NM_003190.5	c.869-126T>A		intron_variant		ENST00000434618.7	NP_003181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7	c.869-126T>A		intron_variant		1	NM_003190.5	ENSP00000395701.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60740 AN: 151850 Hom.: 14099 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.488 AC: 547818 AN: 1123266 Hom.: 137659 Cov.: 16 AF XY: 0.493 AC XY: 274622 AN XY: 557286

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.607

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.400 AC: 60747 AN: 151968 Hom.: 14098 Cov.: 32 AF XY: 0.405 AC XY: 30112 AN XY: 74278

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.397

Alfa AF: 0.445 Hom.: 2007

Bravo AF: 0.379

Asia WGS AF: 0.448 AC: 1559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs1800838; hg19: chr6-33272541; COSMIC: COSV70457689; COSMIC: COSV70457689;