rs3820667

Positions:

• chr1-109425788-A-C
• chr1-109425788-A-G
• chr1-109425788-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000538610.5(PSMA5):​c.-608T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 153,836 control chromosomes in the GnomAD database, including 16,582 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 0.43 (16359 hom., cov: 32)
  • Exomes 𝑓: 0.50 (223 hom.)
• Consequence: PSMA5 ENST00000538610.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA5	NM_002790.4	c.29+514T>G		intron_variant		ENST00000271308.9	NP_002781.2
PSMA5	NM_001199772.2	c.-79+514T>G		intron_variant			NP_001186701.1
PSMA5	NM_001199773.2	c.-146+617T>G		intron_variant			NP_001186702.1
PSMA5	NM_001199774.2	c.-146+632T>G		intron_variant			NP_001186703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA5	ENST00000271308.9	c.29+514T>G		intron_variant		1	NM_002790.4	ENSP00000271308.4

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65801 AN: 151936 Hom.: 16351 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.500 AC: 891 AN: 1782 Hom.: 223 Cov.: 0 AF XY: 0.513 AC XY: 507 AN XY: 988

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.568

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.433 AC: 65821 AN: 152054 Hom.: 16359 Cov.: 32 AF XY: 0.435 AC XY: 32349 AN XY: 74318

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.466

Alfa AF: 0.502 Hom.: 9678

Bravo AF: 0.424

Asia WGS AF: 0.545 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.52

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: rs3820667; hg19: chr1-109968410;