dbSNP rs17588: PSMA4:p.Asp6Asp (chr15-78542191-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.816

Publications

3 publications found

Variant links:

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]

PSMA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA4	NM_002789.6 link	c.18C>T	p.Asp6Asp	synonymous_variant	Exon 3 of 9	ENST00000044462.12	NP_002780.1	P25789-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA4	ENST00000044462.12 link	c.18C>T	p.Asp6Asp	synonymous_variant	Exon 3 of 9	1	NM_002789.6	ENSP00000044462.7		P25789-1

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1719

AN:

152110

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.00130

AC XY:

943

AN XY:

724118

show subpopulations

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:

AN:

39664

South Asian (SAS)

AF:

0.0000948

AC:

AN:

84358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00400

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000253

AC:

281

AN:

1110458

Other (OTH)

AF:

0.00289

AC:

174

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

186

280

373

466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0113

AC:

1723

AN:

152228

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

794

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0383

AC:

1592

AN:

41528

American (AMR)

AF:

0.00425

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68026

Other (OTH)

AF:

0.0114

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00393

Hom.:

Bravo

AF:

0.0122

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.82

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over