Variant 6-3259110-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001128591.2(PSMG4):c.88G>A(p.Val30Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000555 in 1,279,012 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00068 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00054 ( 1 hom. )

Consequence

PSMG4
NM_001128591.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

Variant links:

Genes affected

PSMG4 (HGNC:21108): (proteasome assembly chaperone 4) Predicted to be involved in proteasome assembly. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

PSMG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062268376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMG4	NM_001128591.2 linkuse as main transcript	c.88G>A	p.Val30Ile	missense_variant	1/3	ENST00000438998.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMG4	ENST00000438998.7 linkuse as main transcript	c.88G>A	p.Val30Ile	missense_variant	1/3	2	NM_001128591.2	P1	Q5JS54-1

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00641

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00141

AC:

AN:

21206

Hom.:

AF XY:

0.00156

AC XY:

AN XY:

12154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000795

Gnomad FIN exome

AF:

0.00732

Gnomad NFE exome

AF:

0.000389

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000539

AC:

607

AN:

1126702

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

304

AN XY:

539042

show subpopulations

Gnomad4 AFR exome

AF:

0.0000861

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000616

Gnomad4 FIN exome

AF:

0.00846

Gnomad4 NFE exome

AF:

0.000350

Gnomad4 OTH exome

AF:

0.000463

GnomAD4 genome

AF:

0.000676

AC:

103

AN:

152310

Hom.:

Cov.:

AF XY:

0.000859

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00641

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000318

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.000448

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.88G>A (p.V30I) alteration is located in exon 1 (coding exon 1) of the PSMG4 gene. This alteration results from a G to A substitution at nucleotide position 88, causing the valine (V) at amino acid position 30 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

T;.;.;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.019

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.78

T;T;T;T;T

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.0062

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

M;.;M;M;.

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.53

N;N;N;N;N

REVEL

Benign

0.047

Sift

Benign

0.21

T;D;T;T;D

Sift4G

Uncertain

0.033

D;D;D;D;D

Polyphen

0.014

B;.;.;.;.

Vest4

0.24

MVP

0.014

ClinPred

0.13

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.29

gMVP

0.079

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over