rs12901682

chr15-78540881-A-Cchr15-78540881-A-T

Variant summary

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

The NM_002789.6(PSMA4):c.-24+342A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 152,228 control chromosomes in the GnomAD database, including 67,664 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 0.94 (67625 hom., cov: 30)
  • Exomes 𝑓: 0.98 (39 hom.)
• Consequence: PSMA4 NM_002789.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMA4	NM_002789.6	c.-24+342A>C		intron_variant		ENST00000044462.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMA4	ENST00000044462.12	c.-24+342A>C		intron_variant		1	NM_002789.6	P1

Frequencies

GnomAD3 genomes AF: 0.940 AC: 142943 AN: 152028 Hom.: 67579 Cov.: 30

Gnomad AFR AF: 0.831

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.947

GnomAD4 exome AF: 0.976 AC: 80 AN: 82 Hom.: 39 Cov.: 0 AF XY: 0.955 AC XY: 42 AN XY: 44

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.940 AC: 143045 AN: 152146 Hom.: 67625 Cov.: 30 AF XY: 0.942 AC XY: 70039 AN XY: 74378

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.976

Gnomad4 ASJ AF: 0.974

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.980

Gnomad4 FIN AF: 0.984

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.948

Alfa AF: 0.982 Hom.: 113826

Bravo AF: 0.933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.0
Dann	Benign	0.67

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: rs12901682; hg19: chr15-78833223;