chr6-32845502-C-A

Variant names:

• chr6-32845502-C-A
• rs1057373
• NM_000593.6:c.*77G>T

Variant summary

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

The NM_000593.6(TAP1):​c.*77G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 1,497,186 control chromosomes in the GnomAD database, including 6,750 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 0.082 (584 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6166 hom.)
• Consequence: TAP1 NM_000593.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 38 publications found

Genes affected

TAP1 (HGNC:43): (transporter 1, ATP binding cassette subfamily B member) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

PSMB8-AS1 (HGNC:39758): (PSMB8 antisense RNA 1 (head to head))

PSMB9 (HGNC:9546): (proteasome 20S subunit beta 9) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. [provided by RefSeq, Mar 2010]

PSMB9 Gene-Disease associations (from GenCC):

• proteasome-associated autoinflammatory syndrome 3

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP1	NM_000593.6	c.*77G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000354258.5	NP_000584.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5	c.*77G>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_000593.6	ENSP00000346206.5

Frequencies

GnomAD3 genomes AF: 0.0821 AC: 12494 AN: 152096 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0742

GnomAD4 exome AF: 0.0911 AC: 122579 AN: 1344972 Hom.: 6166 Cov.: 23 AF XY: 0.0932 AC XY: 62813 AN XY: 673660

African (AFR) AF: 0.0444 AC: 1379 AN: 31084

American (AMR) AF: 0.119 AC: 5149 AN: 43168

Ashkenazi Jewish (ASJ) AF: 0.0218 AC: 551 AN: 25238

East Asian (EAS) AF: 0.133 AC: 5161 AN: 38832

South Asian (SAS) AF: 0.152 AC: 12643 AN: 83102

European-Finnish (FIN) AF: 0.142 AC: 7350 AN: 51698

Middle Eastern (MID) AF: 0.125 AC: 690 AN: 5528

European-Non Finnish (NFE) AF: 0.0841 AC: 84908 AN: 1009862

Other (OTH) AF: 0.0841 AC: 4748 AN: 56460

GnomAD4 genome AF: 0.0822 AC: 12519 AN: 152214 Hom.: 584 Cov.: 32 AF XY: 0.0854 AC XY: 6357 AN XY: 74416

African (AFR) AF: 0.0432 AC: 1796 AN: 41534

American (AMR) AF: 0.0774 AC: 1184 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3472

East Asian (EAS) AF: 0.152 AC: 785 AN: 5176

South Asian (SAS) AF: 0.150 AC: 722 AN: 4826

European-Finnish (FIN) AF: 0.140 AC: 1481 AN: 10586

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0907 AC: 6171 AN: 68006

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.0872 Hom.: 2760

Bravo AF: 0.0761

Asia WGS AF: 0.132 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.9
DANN	Benign	0.81
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1057373; hg19: chr6-32813279; COSMIC: COSV62754256; COSMIC: COSV62754256;