NM_002789.6:c.18C>T

Variant names:

• chr15-78542191-C-T
• rs17588
• NM_002789.6:c.18C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_002789.6(PSMA4):​c.18C>T​(p.Asp6Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,608,334 control chromosomes in the GnomAD database, including 78 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 0.011 (48 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (30 hom.)
• Consequence: PSMA4 NM_002789.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.816
• Publications: 3 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.816 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0113 (1723/152228) while in subpopulation AFR AF = 0.0383 (1592/41528). AF 95% confidence interval is 0.0368. There are 48 homozygotes in GnomAd4. There are 794 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 gene

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.18C>T	p.Asp6Asp	synonymous	Exon 3 of 9	NP_002780.1	P25789-1
	PSMA4	NM_001102667.2		c.18C>T	p.Asp6Asp	synonymous	Exon 3 of 9	NP_001096137.1	P25789-1
	PSMA4	NM_001330676.2		c.18C>T	p.Asp6Asp	synonymous	Exon 3 of 9	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.18C>T	p.Asp6Asp	synonymous	Exon 3 of 9	ENSP00000044462.7	P25789-1
	PSMA4	ENST00000413382.6	TSL:1	c.-33C>T		5_prime_UTR	Exon 3 of 8	ENSP00000402118.2	P25789-2
	PSMA4	ENST00000558635.1	TSL:1	n.368C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1719 AN: 152110 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00336 AC: 828 AN: 246196 AF XY: 0.00265

Gnomad AFR exome AF: 0.0369

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.00505

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000445

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00143 AC: 2082 AN: 1456106 Hom.: 30 Cov.: 30 AF XY: 0.00130 AC XY: 943 AN XY: 724118

African (AFR) AF: 0.0393 AC: 1303 AN: 33138

American (AMR) AF: 0.00336 AC: 145 AN: 43126

Ashkenazi Jewish (ASJ) AF: 0.00570 AC: 148 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000948 AC: 8 AN: 84358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00400 AC: 23 AN: 5756

European-Non Finnish (NFE) AF: 0.000253 AC: 281 AN: 1110458

Other (OTH) AF: 0.00289 AC: 174 AN: 60256

GnomAD4 genome AF: 0.0113 AC: 1723 AN: 152228 Hom.: 48 Cov.: 33 AF XY: 0.0107 AC XY: 794 AN XY: 74418

African (AFR) AF: 0.0383 AC: 1592 AN: 41528

American (AMR) AF: 0.00425 AC: 65 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68026

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.00393 Hom.: 11

Bravo AF: 0.0122

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		0.82
Mutation Taster		=95/5	polymorphism

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: rs17588; hg19: chr15-78834533;