rs1059288

Positions:

• chr6-33299895-A-G

Variant summary

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

The NM_003190.5(TAPBP):​c.*1865T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,612 control chromosomes in the GnomAD database, including 27,529 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 0.59 (27432 hom., cov: 31)
  • Exomes 𝑓: 0.51 (97 hom.)
• Consequence: TAPBP NM_003190.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAPBP	NM_003190.5	c.*1865T>C		3_prime_UTR_variant	8/8	ENST00000434618.7	NP_003181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7	c.*1865T>C		3_prime_UTR_variant	8/8	1	NM_003190.5	ENSP00000395701	P2
	ENST00000689186.1	n.417A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90009 AN: 151822 Hom.: 27384 Cov.: 31

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.585

GnomAD4 exome AF: 0.510 AC: 342 AN: 670 Hom.: 97 Cov.: 0 AF XY: 0.508 AC XY: 185 AN XY: 364

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.593 AC: 90111 AN: 151942 Hom.: 27432 Cov.: 31 AF XY: 0.593 AC XY: 44020 AN XY: 74220

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.583

Alfa AF: 0.545 Hom.: 32038

Bravo AF: 0.601

Asia WGS AF: 0.527 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1059288; hg19: chr6-33267672;