rs12529313

Variant names:

• chr6-32849353-A-G
• rs12529313
• NM_000593.6:c.1249-235T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32849353-A-G
• chr6-32849353-A-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.1249-235T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 604,996 control chromosomes in the GnomAD database, including 11,104 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 0.20 (3151 hom., cov: 31)
  • Exomes 𝑓: 0.18 (7953 hom.)
• Consequence: TAP1 NM_000593.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659
• 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]

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP1	NM_000593.6	c.1249-235T>C		intron_variant	Intron 5 of 10	ENST00000354258.5	NP_000584.3
TAP1	NM_001292022.2	c.646-235T>C		intron_variant	Intron 5 of 10		NP_001278951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5	c.1249-235T>C		intron_variant	Intron 5 of 10	1	NM_000593.6	ENSP00000346206.5

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30220 AN: 151958 Hom.: 3128 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.182 AC: 82611 AN: 452920 Hom.: 7953 Cov.: 4 AF XY: 0.185 AC XY: 44589 AN XY: 240708

African (AFR) AF: 0.258 AC: 3243 AN: 12558

American (AMR) AF: 0.179 AC: 3525 AN: 19640

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 2709 AN: 13854

East Asian (EAS) AF: 0.161 AC: 4901 AN: 30466

South Asian (SAS) AF: 0.249 AC: 11424 AN: 45914

European-Finnish (FIN) AF: 0.211 AC: 5937 AN: 28122

Middle Eastern (MID) AF: 0.191 AC: 380 AN: 1992

European-Non Finnish (NFE) AF: 0.167 AC: 45718 AN: 274240

Other (OTH) AF: 0.183 AC: 4774 AN: 26134

GnomAD4 genome AF: 0.199 AC: 30302 AN: 152076 Hom.: 3151 Cov.: 31 AF XY: 0.201 AC XY: 14949 AN XY: 74342

African (AFR) AF: 0.255 AC: 10575 AN: 41436

American (AMR) AF: 0.160 AC: 2439 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 719 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1124 AN: 5178

South Asian (SAS) AF: 0.251 AC: 1213 AN: 4828

European-Finnish (FIN) AF: 0.201 AC: 2122 AN: 10582

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11504 AN: 67986

Other (OTH) AF: 0.179 AC: 377 AN: 2112

Alfa AF: 0.180 Hom.: 5495

Bravo AF: 0.197

Asia WGS AF: 0.250 AC: 867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.80
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12529313; hg19: chr6-32817130;