6-33299895-A-G

Variant names:

• chr6-33299895-A-G
• rs1059288
• NM_003190.5:c.*1865T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 publications found

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]

ENSG00000289100 (HGNC:):

RGL2 (HGNC:9769): (ral guanine nucleotide dissociation stimulator like 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity and small GTPase mediated signal transduction. Predicted to act upstream of or within negative regulation of cardiac muscle cell apoptotic process; positive regulation of phosphatidylinositol 3-kinase signaling; and regulation of Ral protein signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TAPBP	NM_003190.5	c.*1865T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000434618.7	NP_003181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7	c.*1865T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_003190.5	ENSP00000395701.2

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.509 AC: 291 AN: 572

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.554 AC: 41 AN: 74

Other (OTH) AF: 0.125 AC: 1 AN: 8

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

African (AFR) AF: 0.737 AC: 30547 AN: 41470

American (AMR) AF: 0.578 AC: 8822 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2004 AN: 3468

East Asian (EAS) AF: 0.403 AC: 2065 AN: 5122

South Asian (SAS) AF: 0.651 AC: 3130 AN: 4808

European-Finnish (FIN) AF: 0.527 AC: 5551 AN: 10538

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36240 AN: 67950

Other (OTH) AF: 0.583 AC: 1229 AN: 2108

Alfa AF: 0.553 Hom.: 86601

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
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1059288; hg19: chr6-33267672;