Genetic Variant ENST00000558635.1:n.32T>C (chr15-78540490-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000558635.1(PSMA4):n.32T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,372 control chromosomes in the GnomAD database, including 6,558 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 0.28 ( 6554 hom., cov: 33)

Exomes 𝑓: 0.18 ( 4 hom. )

Consequence

PSMA4
ENST00000558635.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.78

Publications

31 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:

ENSG00000297479 (HGNC:):

ENSG00000297479 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA4	NM_002789.6 link	c.-73T>C		5_prime_UTR_variant	Exon 1 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.-73T>C		5_prime_UTR_variant	Exon 1 of 9	1	NM_002789.6	ENSP00000044462.7		P25789-1

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

42025

AN:

152110

Hom.:

6539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.286

GnomAD4 exome

AF:

0.181

AC:

AN:

144

Hom.:

Cov.:

AF XY:

0.179

AC XY:

AN XY:

106

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.175

AC:

AN:

126

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.276

AC:

42069

AN:

152228

Hom.:

6554

Cov.:

AF XY:

0.284

AC XY:

21141

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.270

AC:

11199

AN:

41546

American (AMR)

AF:

0.469

AC:

7182

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

824

AN:

3472

East Asian (EAS)

AF:

0.442

AC:

2285

AN:

5170

South Asian (SAS)

AF:

0.395

AC:

1906

AN:

4824

European-Finnish (FIN)

AF:

0.279

AC:

2953

AN:

10602

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14868

AN:

67992

Other (OTH)

AF:

0.290

AC:

611

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1554

3108

4663

6217

7771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.240

Hom.:

1157

Bravo

AF:

0.289

Asia WGS

AF:

0.408

AC:

1416

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.62

(source)

DANN

Benign

0.65

PhyloP100

-1.8

PromoterAI

0.0054

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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