rs17586966

chr1-109412947-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PSMA5	NM_002790.4	c.291+121A>G		intron_variant		ENST00000271308.9
PSMA5	NM_001199772.2	c.117+121A>G		intron_variant
PSMA5	NM_001199773.2	c.117+121A>G		intron_variant
PSMA5	NM_001199774.2	c.117+121A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMA5	ENST00000271308.9	c.291+121A>G		intron_variant		1	NM_002790.4	P1
PSMA5	ENST00000538610.5	c.117+121A>G		intron_variant		1
PSMA5	ENST00000490870.5	n.1069+121A>G		intron_variant, non_coding_transcript_variant		1
PSMA5	ENST00000484563.1	n.509A>G		non_coding_transcript_exon_variant	4/4	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

Gnomad4 AFR exome AF: 0.0402

Gnomad4 AMR exome AF: 0.0146

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.000484

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.0703

Gnomad4 NFE exome AF: 0.0618

Gnomad4 OTH exome AF: 0.0481

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

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.0618

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0530 Hom.: 300

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

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: rs17586966; hg19: chr1-109955569;