rs3813571

Positions:

• chr15-78540450-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002789.6(PSMA4):​c.-113G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,410 control chromosomes in the GnomAD database, including 8,598 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 0.31 (8583 hom., cov: 33)
  • Exomes 𝑓: 0.38 (15 hom.)
• Consequence: PSMA4 NM_002789.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA4	NM_002789.6	c.-113G>T		5_prime_UTR_variant	1/9	ENST00000044462.12	NP_002780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA4	ENST00000044462.12	c.-113G>T		5_prime_UTR_variant	1/9	1	NM_002789.6	ENSP00000044462	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47930 AN: 152114 Hom.: 8586 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.376 AC: 67 AN: 178 Hom.: 15 Cov.: 0 AF XY: 0.379 AC XY: 50 AN XY: 132

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.315 AC: 47939 AN: 152232 Hom.: 8583 Cov.: 33 AF XY: 0.312 AC XY: 23237 AN XY: 74450

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.317

Alfa AF: 0.385 Hom.: 13415

Bravo AF: 0.299

Asia WGS AF: 0.271 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs3813571; hg19: chr15-78832792;