Variant 6-3259074-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001128591.2(PSMG4):c.52A>G(p.Ser18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000473 in 1,268,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

PSMG4
NM_001128591.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40798336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMG4	NM_001128591.2 linkuse as main transcript	c.52A>G	p.Ser18Gly	missense_variant	1/3	ENST00000438998.7	NP_001122063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMG4	ENST00000438998.7 linkuse as main transcript	c.52A>G	p.Ser18Gly	missense_variant	1/3	2	NM_001128591.2	ENSP00000413353	P1	Q5JS54-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152018

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:

0.000387

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

AF:

0.00000358

AC:

AN:

1115930

Hom.:

Cov.:

AF XY:

0.00000188

AC XY:

AN XY:

531700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000375

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000320

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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 17, 2021

The c.52A>G (p.S18G) alteration is located in exon 1 (coding exon 1) of the PSMG4 gene. This alteration results from a A to G substitution at nucleotide position 52, causing the serine (S) at amino acid position 18 to be replaced by a glycine (G). 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

0.45

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.;.;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.80

T;T;T;T;T

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.41

T;T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.8

M;.;M;M;.

MutationTaster

Benign

0.98

D;D;D;D;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.3

N;D;N;D;D

REVEL

Benign

0.16

Sift

Benign

0.040

D;D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D

Polyphen

0.96

D;.;.;.;.

Vest4

0.22

MutPred

0.27

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.014

ClinPred

0.93

GERP RS

4.8

Varity_R

0.47

gMVP

0.18

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