rs17588

chr15-78542191-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_002789.6(PSMA4):c.18C>T(p.Asp6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,608,334 control chromosomes in the GnomAD database, including 78 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 0.011 (48 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (30 hom.)
• Consequence: PSMA4 NM_002789.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.816

Genes affected

PSMA4 (HGNC:9533): (proteasome 20S subunit alpha 4) This gene encodes a core alpha subunit of the 20S proteosome, which is a highly ordered ring-shaped structure composed of four rings of 28 non-identical subunits. Proteasomes cleave peptides in an ATP- and ubiquitin-dependent manner. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.816 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1723/152228) while in subpopulation AFR AF= 0.0383 (1592/41528). AF 95% confidence interval is 0.0368. There are 48 homozygotes in gnomad4. There are 794 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 48 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMA4	NM_002789.6	c.18C>T	p.Asp6=	synonymous_variant	3/9	ENST00000044462.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMA4	ENST00000044462.12	c.18C>T	p.Asp6=	synonymous_variant	3/9	1	NM_002789.6	P1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1719 AN: 152110 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00336 AC: 828 AN: 246196 Hom.: 11 AF XY: 0.00265 AC XY: 352 AN XY: 132928

Gnomad AFR exome AF: 0.0369

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.00505

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000445

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00143 AC: 2082 AN: 1456106 Hom.: 30 Cov.: 30 AF XY: 0.00130 AC XY: 943 AN XY: 724118

Gnomad4 AFR exome AF: 0.0393

Gnomad4 AMR exome AF: 0.00336

Gnomad4 ASJ exome AF: 0.00570

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000948

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000253

Gnomad4 OTH exome AF: 0.00289

GnomAD4 genome AF: 0.0113 AC: 1723 AN: 152228 Hom.: 48 Cov.: 33 AF XY: 0.0107 AC XY: 794 AN XY: 74418

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00441 Hom.: 10

Bravo AF: 0.0122

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	11
Dann	Benign	0.84

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: rs17588; hg19: chr15-78834533;