Variant 6-3259039-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001128591.2(PSMG4):c.17T>C(p.Val6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PSMG4
NM_001128591.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.674

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038975745).

BP6

Variant 6-3259039-T-C is Benign according to our data. Variant chr6-3259039-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3311050.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMG4	NM_001128591.2 linkuse as main transcript	c.17T>C	p.Val6Ala	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.17T>C	p.Val6Ala	missense_variant	1/3	2	NM_001128591.2	ENSP00000413353	P1	Q5JS54-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1098574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

521254

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.7

DANN

Benign

0.53

DEOGEN2

Benign

0.0021

T;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.35

T;T;T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.039

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.4

N;.;N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.94

N;N;N;N;N

REVEL

Benign

0.035

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;.;.;.;.

Vest4

0.053

MutPred

0.34

Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);

MVP

0.014

ClinPred

0.055

GERP RS

3.0

Varity_R

0.038

gMVP

0.075

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