rs3106189

Variant names:

• chr6-33314225-C-T
• rs3106189
• ENST00000489157.6:c.-184G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000489157.6(TAPBP):​c.-184G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 775,622 control chromosomes in the GnomAD database, including 101,434 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 0.52 (20515 hom., cov: 28)
  • Exomes 𝑓: 0.50 (80919 hom.)
• Consequence: TAPBP ENST00000489157.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 28 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]

ZBTB22 (HGNC:13085): (zinc finger and BTB domain containing 22) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAPBP	NM_003190.5	c.-184G>A		upstream_gene_variant		ENST00000434618.7	NP_003181.3
ZBTB22	NM_005453.5	c.*787G>A		downstream_gene_variant		ENST00000431845.3	NP_005444.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7	c.-184G>A		upstream_gene_variant		1	NM_003190.5	ENSP00000395701.2
ZBTB22	ENST00000431845.3	c.*787G>A		downstream_gene_variant		1	NM_005453.5	ENSP00000407545.2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78370 AN: 151094 Hom.: 20483 Cov.: 28

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.503 AC: 313971 AN: 624414 Hom.: 80919 Cov.: 8 AF XY: 0.510 AC XY: 163302 AN XY: 320368

African (AFR) AF: 0.556 AC: 9017 AN: 16222

American (AMR) AF: 0.543 AC: 12734 AN: 23458

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 8245 AN: 15264

East Asian (EAS) AF: 0.335 AC: 10653 AN: 31798

South Asian (SAS) AF: 0.624 AC: 32578 AN: 52202

European-Finnish (FIN) AF: 0.524 AC: 15688 AN: 29962

Middle Eastern (MID) AF: 0.494 AC: 1145 AN: 2320

European-Non Finnish (NFE) AF: 0.493 AC: 207575 AN: 421306

Other (OTH) AF: 0.512 AC: 16336 AN: 31882

GnomAD4 genome AF: 0.519 AC: 78457 AN: 151208 Hom.: 20515 Cov.: 28 AF XY: 0.522 AC XY: 38531 AN XY: 73828

African (AFR) AF: 0.547 AC: 22473 AN: 41120

American (AMR) AF: 0.527 AC: 8010 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1883 AN: 3464

East Asian (EAS) AF: 0.358 AC: 1836 AN: 5128

South Asian (SAS) AF: 0.614 AC: 2944 AN: 4796

European-Finnish (FIN) AF: 0.521 AC: 5417 AN: 10404

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34352 AN: 67798

Other (OTH) AF: 0.506 AC: 1057 AN: 2090

Alfa AF: 0.511 Hom.: 52727

Bravo AF: 0.517

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.1
DANN	Benign	0.69
PhyloP100		-1.5
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3106189; hg19: chr6-33282002;