Variant 2-53892888-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014614.3(PSME4):c.4111T>A(p.Ser1371Thr) variant causes a missense change. The variant allele was found at a frequency of 0.306 in 1,612,804 control chromosomes in the GnomAD database, including 77,625 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.28 ( 6554 hom., cov: 32)

Exomes 𝑓: 0.31 ( 71071 hom. )

Consequence

PSME4
NM_014614.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.96

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.8584085E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSME4	NM_014614.3 linkuse as main transcript	c.4111T>A	p.Ser1371Thr	missense_variant	36/47	ENST00000404125.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSME4	ENST00000404125.6 linkuse as main transcript	c.4111T>A	p.Ser1371Thr	missense_variant	36/47	1	NM_014614.3	P1	Q14997-1
PSME4	ENST00000389993.7 linkuse as main transcript	c.*2244T>A		3_prime_UTR_variant, NMD_transcript_variant	35/46	1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43191

AN:

151884

Hom.:

6550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.471

Gnomad FIN

AF:

0.359

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.267

GnomAD3 exomes

AF:

0.321

AC:

80529

AN:

250734

Hom.:

13774

AF XY:

0.330

AC XY:

44695

AN XY:

135474

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.333

Gnomad EAS exome

AF:

0.453

Gnomad SAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.369

Gnomad NFE exome

AF:

0.293

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.308

AC:

449791

AN:

1460802

Hom.:

71071

Cov.:

AF XY:

0.312

AC XY:

226933

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.384

Gnomad4 SAS exome

AF:

0.453

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.296

Gnomad4 OTH exome

AF:

0.323

GnomAD4 genome

AF:

0.284

AC:

43219

AN:

152002

Hom.:

6554

Cov.:

AF XY:

0.292

AC XY:

21656

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.267

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.471

Gnomad4 FIN

AF:

0.359

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.269

Alfa

AF:

0.283

Hom.:

4935

Bravo

AF:

0.269

TwinsUK

AF:

0.299

AC:

1110

ALSPAC

AF:

0.306

AC:

1179

ESP6500AA

AF:

0.211

AC:

931

ESP6500EA

AF:

0.302

AC:

2595

ExAC

AF:

0.320

AC:

38865

Asia WGS

AF:

0.478

AC:

1659

AN:

3476

EpiCase

AF:

0.285

EpiControl

AF:

0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.081

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.0045

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

MetaRNN

Benign

0.00069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

MutationTaster

Benign

0.00023

P;P

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.87

REVEL

Benign

0.10

Sift

Benign

0.57

Sift4G

Benign

0.82

Polyphen

0.0020

Vest4

0.052

MPC

0.24

ClinPred

0.023

GERP RS

5.4

Varity_R

0.22

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over