rs2348071

Variant names:

• chr14-58263908-A-G
• rs2348071
• NM_002788.4:c.543+138A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PSMA3	NM_002788.4	c.543+138A>G		intron_variant	Intron 7 of 10	ENST00000216455.9	NP_002779.1
PSMA3	NM_152132.3	c.522+138A>G		intron_variant	Intron 7 of 10		NP_687033.1
PSMA3	NR_038123.2	n.538+138A>G		intron_variant	Intron 6 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA3	ENST00000216455.9	c.543+138A>G		intron_variant	Intron 7 of 10	1	NM_002788.4	ENSP00000216455.4

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

African (AFR) AF: 0.723 AC: 9775 AN: 13522

American (AMR) AF: 0.665 AC: 14254 AN: 21432

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 12370 AN: 15230

East Asian (EAS) AF: 0.385 AC: 12148 AN: 31558

South Asian (SAS) AF: 0.705 AC: 35218 AN: 49972

European-Finnish (FIN) AF: 0.631 AC: 28753 AN: 45540

Middle Eastern (MID) AF: 0.841 AC: 2387 AN: 2838

European-Non Finnish (NFE) AF: 0.728 AC: 229226 AN: 314952

Other (OTH) AF: 0.710 AC: 19678 AN: 27720

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

African (AFR) AF: 0.713 AC: 29595 AN: 41498

American (AMR) AF: 0.700 AC: 10686 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2850 AN: 3472

East Asian (EAS) AF: 0.407 AC: 2098 AN: 5158

South Asian (SAS) AF: 0.685 AC: 3301 AN: 4816

European-Finnish (FIN) AF: 0.629 AC: 6634 AN: 10542

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49122 AN: 67962

Other (OTH) AF: 0.721 AC: 1518 AN: 2104

Alfa AF: 0.709 Hom.: 4923

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
PhyloP100		0.039
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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