rs55702652

Variant names:

• chr6-32853214-A-G
• rs55702652
• NM_000593.6:c.423T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32853214-A-G
• chr6-32853214-A-C
• chr6-32853214-A-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000593.6(TAP1):​c.423T>C​(p.Val141Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 1,611,216 control chromosomes in the GnomAD database, including 955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (90 hom., cov: 32)
  • Exomes 𝑓: 0.031 (865 hom.)
• Consequence: TAP1 NM_000593.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0880
• Publications: 4 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]

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 6-32853214-A-G is Benign according to our data. Variant chr6-32853214-A-G is described in ClinVar as Benign. ClinVar VariationId is 466389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.088 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0603 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP1	NM_000593.6	MANE Select	c.423T>C	p.Val141Val	synonymous	Exon 1 of 11	NP_000584.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP1	ENST00000354258.5	TSL:1 MANE Select	c.423T>C	p.Val141Val	synonymous	Exon 1 of 11	ENSP00000346206.5	Q03518-1
	TAP1	ENST00000698423.1		c.423T>C	p.Val141Val	synonymous	Exon 1 of 12	ENSP00000513711.1	A0A8V8TM76
	TAP1	ENST00000920268.1		c.423T>C	p.Val141Val	synonymous	Exon 1 of 11	ENSP00000590327.1

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4624 AN: 152176 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.0360

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.0311 AC: 7513 AN: 241300 AF XY: 0.0329

Gnomad AFR exome AF: 0.0319

Gnomad AMR exome AF: 0.0139

Gnomad ASJ exome AF: 0.00967

Gnomad EAS exome AF: 0.000774

Gnomad FIN exome AF: 0.0357

Gnomad NFE exome AF: 0.0342

Gnomad OTH exome AF: 0.0277

GnomAD4 exome AF: 0.0313 AC: 45608 AN: 1458922 Hom.: 865 Cov.: 32 AF XY: 0.0324 AC XY: 23474 AN XY: 725576

African (AFR) AF: 0.0339 AC: 1135 AN: 33452

American (AMR) AF: 0.0142 AC: 631 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 280 AN: 26060

East Asian (EAS) AF: 0.000706 AC: 28 AN: 39674

South Asian (SAS) AF: 0.0617 AC: 5295 AN: 85850

European-Finnish (FIN) AF: 0.0341 AC: 1780 AN: 52184

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5766

European-Non Finnish (NFE) AF: 0.0313 AC: 34738 AN: 1111152

Other (OTH) AF: 0.0278 AC: 1674 AN: 60300

GnomAD4 genome AF: 0.0304 AC: 4626 AN: 152294 Hom.: 90 Cov.: 32 AF XY: 0.0308 AC XY: 2291 AN XY: 74464

African (AFR) AF: 0.0318 AC: 1321 AN: 41562

American (AMR) AF: 0.0157 AC: 240 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5184

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4826

European-Finnish (FIN) AF: 0.0360 AC: 382 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0331 AC: 2250 AN: 68016

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.0303 Hom.: 167

Bravo AF: 0.0281

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MHC class I deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.3
DANN	Benign	0.59
PhyloP100		0.088
PromoterAI		0.047	Neutral
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: rs55702652; hg19: chr6-32820991; COSMIC: COSV107445379; COSMIC: COSV107445379;