15-78541488-C-G

Variant names:

• chr15-78541488-C-G
• rs4243083
• NM_002789.6:c.-23-417C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002789.6(PSMA4):​c.-23-417C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 196,338 control chromosomes in the GnomAD database, including 42,230 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 0.66 (33744 hom., cov: 31)
  • Exomes 𝑓: 0.61 (8486 hom.)
• Consequence: PSMA4 NM_002789.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002789.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA4	NM_002789.6	MANE Select	c.-23-417C>G		intron	N/A	NP_002780.1	P25789-1
	PSMA4	NM_001102667.2		c.-23-417C>G		intron	N/A	NP_001096137.1	P25789-1
	PSMA4	NM_001330676.2		c.-23-417C>G		intron	N/A	NP_001317605.1	P25789-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA4	ENST00000044462.12	TSL:1 MANE Select	c.-23-417C>G		intron	N/A	ENSP00000044462.7	P25789-1
	PSMA4	ENST00000413382.6	TSL:1	c.-73-417C>G		intron	N/A	ENSP00000402118.2	P25789-2
	PSMA4	ENST00000559934.5	TSL:1	n.1045C>G		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100341 AN: 151968 Hom.: 33706 Cov.: 31

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.609 AC: 26941 AN: 44252 Hom.: 8486 Cov.: 0 AF XY: 0.613 AC XY: 14525 AN XY: 23706

African (AFR) AF: 0.744 AC: 229 AN: 308

American (AMR) AF: 0.762 AC: 2282 AN: 2994

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 442 AN: 674

East Asian (EAS) AF: 0.889 AC: 542 AN: 610

South Asian (SAS) AF: 0.659 AC: 5330 AN: 8082

European-Finnish (FIN) AF: 0.605 AC: 1310 AN: 2166

Middle Eastern (MID) AF: 0.757 AC: 106 AN: 140

European-Non Finnish (NFE) AF: 0.567 AC: 15266 AN: 26908

Other (OTH) AF: 0.605 AC: 1434 AN: 2370

GnomAD4 genome AF: 0.660 AC: 100440 AN: 152086 Hom.: 33744 Cov.: 31 AF XY: 0.665 AC XY: 49443 AN XY: 74350

African (AFR) AF: 0.751 AC: 31156 AN: 41498

American (AMR) AF: 0.744 AC: 11363 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2244 AN: 3470

East Asian (EAS) AF: 0.836 AC: 4329 AN: 5180

South Asian (SAS) AF: 0.667 AC: 3218 AN: 4822

European-Finnish (FIN) AF: 0.628 AC: 6640 AN: 10572

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39333 AN: 67954

Other (OTH) AF: 0.668 AC: 1405 AN: 2104

Alfa AF: 0.468 Hom.: 1186

Bravo AF: 0.672

Asia WGS AF: 0.727 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.50
PhyloP100		-1.7
PromoterAI		-0.039	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4243083; hg19: chr15-78833830;