dbSNP rs805408: PSME4:p.Ser1371Ala (chr2-53892888-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014614.3(PSME4):c.4111T>G(p.Ser1371Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PSME4
NM_014614.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.96

Publications

32 publications found

Variant links:

Genes affected

PSME4 (HGNC:20635): (proteasome activator subunit 4) Predicted to enable lysine-acetylated histone binding activity; peptidase activator activity; and proteasome binding activity. Predicted to be involved in DNA repair; proteasomal ubiquitin-independent protein catabolic process; and spermatogenesis, exchange of chromosomal proteins. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PSME4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27364925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSME4	NM_014614.3 link	c.4111T>G	p.Ser1371Ala	missense_variant	Exon 36 of 47	ENST00000404125.6	NP_055429.2	Q14997-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PSME4	ENST00000404125.6 link	c.4111T>G	p.Ser1371Ala	missense_variant	Exon 36 of 47	1	NM_014614.3	ENSP00000384211.1	Q14997-1
PSME4	ENST00000389993.7 link	n.*2244T>G		non_coding_transcript_exon_variant	Exon 35 of 46	1		ENSP00000374643.3	F8WBH5
PSME4	ENST00000389993.7 link	n.*2244T>G		3_prime_UTR_variant	Exon 35 of 46	1		ENSP00000374643.3	F8WBH5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727024

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111814

Other (OTH)

AF:

0.00

AC:

AN:

60382

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41362

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

4935

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.16

Eigen_PC

Benign

0.053

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

M_CAP

Benign

0.019

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.95

PhyloP100

5.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.2

REVEL

Benign

0.069

Sift

Benign

0.52

Sift4G

Benign

0.44

Polyphen

0.0020

Vest4

0.28

MutPred

0.28

Gain of helix (P = 0.0496);

MVP

0.11

MPC

0.22

ClinPred

0.56

GERP RS

5.4

Varity_R

0.18

gMVP

0.079

Mutation Taster

=96/4

polymorphism

(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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rs805408

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over