rs17586966

Variant names:

• chr1-109412947-T-C
• rs17586966
• NM_002790.4:c.291+121A>G

Variant summary

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

The NM_002790.4(PSMA5):​c.291+121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 789,858 control chromosomes in the GnomAD database, including 1,356 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 0.050 (210 hom., cov: 32)
  • Exomes 𝑓: 0.054 (1146 hom.)
• Consequence: PSMA5 NM_002790.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 15 publications found

Genes affected

PSMA5 (HGNC:9534): (proteasome 20S subunit alpha 5) 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 peptidase T1A family, that is a 20S core alpha subunit. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA5	NM_002790.4	c.291+121A>G		intron_variant	Intron 4 of 8	ENST00000271308.9	NP_002781.2
PSMA5	NM_001199772.2	c.117+121A>G		intron_variant	Intron 3 of 7		NP_001186701.1
PSMA5	NM_001199773.2	c.117+121A>G		intron_variant	Intron 4 of 8		NP_001186702.1
PSMA5	NM_001199774.2	c.117+121A>G		intron_variant	Intron 4 of 8		NP_001186703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA5	ENST00000271308.9	c.291+121A>G		intron_variant	Intron 4 of 8	1	NM_002790.4	ENSP00000271308.4
PSMA5	ENST00000538610.5	c.117+121A>G		intron_variant	Intron 4 of 8	1		ENSP00000440618.1
PSMA5	ENST00000490870.5	n.1069+121A>G		intron_variant	Intron 4 of 8	1
PSMA5	ENST00000484563.1	n.509A>G		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7550 AN: 151960 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0233

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0540 AC: 34446 AN: 637782 Hom.: 1146 Cov.: 9 AF XY: 0.0544 AC XY: 18191 AN XY: 334164

African (AFR) AF: 0.0402 AC: 635 AN: 15794

American (AMR) AF: 0.0146 AC: 381 AN: 26140

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 190 AN: 16116

East Asian (EAS) AF: 0.000484 AC: 16 AN: 33032

South Asian (SAS) AF: 0.0560 AC: 2869 AN: 51222

European-Finnish (FIN) AF: 0.0703 AC: 3125 AN: 44448

Middle Eastern (MID) AF: 0.0155 AC: 61 AN: 3936

European-Non Finnish (NFE) AF: 0.0618 AC: 25616 AN: 414804

Other (OTH) AF: 0.0481 AC: 1553 AN: 32290

GnomAD4 genome AF: 0.0497 AC: 7558 AN: 152076 Hom.: 210 Cov.: 32 AF XY: 0.0512 AC XY: 3804 AN XY: 74332

African (AFR) AF: 0.0417 AC: 1729 AN: 41476

American (AMR) AF: 0.0233 AC: 356 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0549 AC: 264 AN: 4812

European-Finnish (FIN) AF: 0.0774 AC: 818 AN: 10566

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0618 AC: 4200 AN: 67980

Other (OTH) AF: 0.0322 AC: 68 AN: 2114

Alfa AF: 0.0524 Hom.: 382

Bravo AF: 0.0433

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		-0.024
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: rs17586966; hg19: chr1-109955569;