chr6-32852191-G-A

Position:

• chr6-32852191-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000593.6(TAP1):​c.762C>T​(p.Gly254Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 1,612,982 control chromosomes in the GnomAD database, including 946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (82 hom., cov: 32)
  • Exomes 𝑓: 0.031 (864 hom.)
• Consequence: TAP1 NM_000593.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91

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]

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]

TAP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 6-32852191-G-A is Benign according to our data. Variant chr6-32852191-G-A is described in ClinVar as [Benign]. Clinvar id is 466393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.91 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP1	NM_000593.6	c.762C>T	p.Gly254Gly	synonymous_variant	3/11	ENST00000354258.5	NP_000584.3
TAP1	NM_001292022.2	c.159C>T	p.Gly53Gly	synonymous_variant	3/11		NP_001278951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5	c.762C>T	p.Gly254Gly	synonymous_variant	3/11	1	NM_000593.6	ENSP00000346206.5

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4536 AN: 152088 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0173

GnomAD3 exomes AF: 0.0313 AC: 7726 AN: 246750 Hom.: 199 AF XY: 0.0330 AC XY: 4441 AN XY: 134460

Gnomad AFR exome AF: 0.0321

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.00963

Gnomad EAS exome AF: 0.000821

Gnomad SAS exome AF: 0.0636

Gnomad FIN exome AF: 0.0355

Gnomad NFE exome AF: 0.0342

Gnomad OTH exome AF: 0.0276

GnomAD4 exome AF: 0.0310 AC: 45231 AN: 1460776 Hom.: 864 Cov.: 33 AF XY: 0.0320 AC XY: 23290 AN XY: 726698

Gnomad4 AFR exome AF: 0.0337

Gnomad4 AMR exome AF: 0.0141

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.000730

Gnomad4 SAS exome AF: 0.0623

Gnomad4 FIN exome AF: 0.0341

Gnomad4 NFE exome AF: 0.0308

Gnomad4 OTH exome AF: 0.0276

GnomAD4 genome AF: 0.0298 AC: 4539 AN: 152206 Hom.: 82 Cov.: 32 AF XY: 0.0302 AC XY: 2247 AN XY: 74416

Gnomad4 AFR AF: 0.0315

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0521

Gnomad4 FIN AF: 0.0359

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0303 Hom.: 86

Bravo AF: 0.0276

Asia WGS AF: 0.0470 AC: 164 AN: 3478

EpiCase AF: 0.0303

EpiControl AF: 0.0292

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class I deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.2
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs41549617; hg19: chr6-32819968;