rs3813570

Positions:

• chr15-78540490-T-C

Variant summary

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

The NM_002789.6(PSMA4):​c.-73T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,372 control chromosomes in the GnomAD database, including 6,558 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 0.28 (6554 hom., cov: 33)
  • Exomes 𝑓: 0.18 (4 hom.)
• Consequence: PSMA4 NM_002789.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMA4	NM_002789.6	c.-73T>C		5_prime_UTR_variant	1/9	ENST00000044462.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMA4	ENST00000044462.12	c.-73T>C		5_prime_UTR_variant	1/9	1	NM_002789.6	P1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 42025 AN: 152110 Hom.: 6539 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.181 AC: 26 AN: 144 Hom.: 4 Cov.: 0 AF XY: 0.179 AC XY: 19 AN XY: 106

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.276 AC: 42069 AN: 152228 Hom.: 6554 Cov.: 33 AF XY: 0.284 AC XY: 21141 AN XY: 74416

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.290

Alfa AF: 0.240 Hom.: 1157

Bravo AF: 0.289

Asia WGS AF: 0.408 AC: 1416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.62
DANN	Benign	0.65
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3813570; hg19: chr15-78832832; COSMIC: COSV50385294; COSMIC: COSV50385294;