rs2348071

Positions:

• chr14-58263908-A-G

Variant summary

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

The NM_002788.4(PSMA3):​c.543+138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 674,790 control chromosomes in the GnomAD database, including 167,452 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 0.70 (37955 hom., cov: 32)
  • Exomes 𝑓: 0.70 (129497 hom.)
• Consequence: PSMA3 NM_002788.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

Genes affected

PSMA3 (HGNC:9532): (proteasome 20S subunit alpha 3) 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. Two alternative transcripts encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ARMH4 (HGNC:19846): (armadillo like helical domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA3	NM_002788.4	c.543+138A>G		intron_variant		ENST00000216455.9	NP_002779.1
PSMA3	NM_152132.3	c.522+138A>G		intron_variant			NP_687033.1
PSMA3	NR_038123.2	n.538+138A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA3	ENST00000216455.9	c.543+138A>G		intron_variant		1	NM_002788.4	ENSP00000216455	P4

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106831 AN: 151908 Hom.: 37942 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.696 AC: 363809 AN: 522764 Hom.: 129497 AF XY: 0.698 AC XY: 193082 AN XY: 276534

Gnomad4 AFR exome AF: 0.723

Gnomad4 AMR exome AF: 0.665

Gnomad4 ASJ exome AF: 0.812

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.705

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.728

Gnomad4 OTH exome AF: 0.710

GnomAD4 genome AF: 0.703 AC: 106886 AN: 152026 Hom.: 37955 Cov.: 32 AF XY: 0.699 AC XY: 51933 AN XY: 74284

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.721

Alfa AF: 0.709 Hom.: 4741

Bravo AF: 0.710

Asia WGS AF: 0.533 AC: 1851 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.33

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: rs2348071; hg19: chr14-58730626; COSMIC: COSV53618528; COSMIC: COSV53618528;