6-32845437-G-A

Variant names:

• chr6-32845437-G-A
• rs3198005
• NM_000593.6:c.*142C>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.*142C>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 0.0407 in 793,664 control chromosomes in the GnomAD database, including 884 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 0.035 (136 hom., cov: 32)
  • Exomes 𝑓: 0.042 (748 hom.)
• Consequence: TAP1 NM_000593.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689
• Publications: 26 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000593.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP1	NM_000593.6	MANE Select	c.*142C>T		3_prime_UTR	Exon 11 of 11	NP_000584.3
	PSMB8-AS1	NR_037173.1		n.435G>A		non_coding_transcript_exon	Exon 3 of 3
	PSMB8-AS1	NR_037174.1		n.297G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP1	ENST00000354258.5	TSL:1 MANE Select	c.*142C>T		3_prime_UTR	Exon 11 of 11	ENSP00000346206.5
	TAP1	ENST00000698423.1		c.2484C>T	p.Ser828Ser	synonymous	Exon 12 of 12	ENSP00000513711.1
	PSMB8-AS1	ENST00000412095.1	TSL:2	n.757G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5259 AN: 152108 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.00896

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.0421 AC: 27008 AN: 641438 Hom.: 748 Cov.: 8 AF XY: 0.0415 AC XY: 14164 AN XY: 341046

African (AFR) AF: 0.00798 AC: 135 AN: 16908

American (AMR) AF: 0.0231 AC: 771 AN: 33448

Ashkenazi Jewish (ASJ) AF: 0.0237 AC: 479 AN: 20174

East Asian (EAS) AF: 0.00117 AC: 38 AN: 32426

South Asian (SAS) AF: 0.0204 AC: 1313 AN: 64290

European-Finnish (FIN) AF: 0.0375 AC: 1505 AN: 40094

Middle Eastern (MID) AF: 0.0354 AC: 143 AN: 4042

European-Non Finnish (NFE) AF: 0.0536 AC: 21259 AN: 396906

Other (OTH) AF: 0.0412 AC: 1365 AN: 33150

GnomAD4 genome AF: 0.0346 AC: 5260 AN: 152226 Hom.: 136 Cov.: 32 AF XY: 0.0341 AC XY: 2540 AN XY: 74418

African (AFR) AF: 0.00891 AC: 370 AN: 41530

American (AMR) AF: 0.0362 AC: 554 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3468

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5178

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4822

European-Finnish (FIN) AF: 0.0338 AC: 358 AN: 10600

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0544 AC: 3700 AN: 68016

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0456 Hom.: 615

Bravo AF: 0.0330

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.85
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs3198005; hg19: chr6-32813214;