Variant chr3-64010930-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP4_ModerateBS2

The NM_014814.3(PSMD6):c.1021G>A(p.Gly341Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,608,974 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 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 2 hom. )

Consequence

PSMD6
NM_014814.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

PSMD6 (HGNC:9564): (proteasome 26S subunit, non-ATPase 6) This gene encodes a member of the protease subunit S10 family. The encoded protein is a subunit of the 26S proteasome which colocalizes with DNA damage foci and is involved in the ATP-dependent degradation of ubiquinated proteins. Alternative splicing results in multiple transcript variants [provided by RefSeq, Nov 2012]

PSMD6 links:

PSMD6 (HGNC:):

PSMD6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, Cadd, Dann, Eigen, phyloP100way_vertebrate, PrimateAI, PROVEAN [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.17036352).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD6	NM_014814.3 linkuse as main transcript	c.1021G>A	p.Gly341Arg	missense_variant	7/8	ENST00000295901.9	NP_055629.1	Q15008-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD6	ENST00000295901.9 linkuse as main transcript	c.1021G>A	p.Gly341Arg	missense_variant	7/8	1	NM_014814.3	ENSP00000295901.4		Q15008-1

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

151858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000799

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00114

AC:

284

AN:

248556

Hom.:

AF XY:

0.00113

AC XY:

152

AN XY:

134406

show subpopulations

Gnomad AFR exome

AF:

0.000747

Gnomad AMR exome

AF:

0.000970

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00155

Gnomad NFE exome

AF:

0.00160

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00155

AC:

2252

AN:

1456998

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1071

AN XY:

724954

show subpopulations

Gnomad4 AFR exome

AF:

0.000721

Gnomad4 AMR exome

AF:

0.000766

Gnomad4 ASJ exome

AF:

0.00154

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00143

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00124

AC:

188

AN:

151976

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000797

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.00117

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00112

AC:

136

EpiCase

AF:

0.00142

EpiControl

AF:

0.00148

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

Aug 16, 2021

The c.1021G>A (p.G341R) alteration is located in exon 7 (coding exon 7) of the PSMD6 gene. This alteration results from a G to A substitution at nucleotide position 1021, causing the glycine (G) at amino acid position 341 to be replaced by an arginine (R). 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

Pathogenic

0.95

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

T;.;.;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.8

M;.;.;.

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-7.1

D;D;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.83

MutPred

0.70

Loss of methylation at R342 (P = 0.0372);.;.;.;

MVP

0.57

MPC

1.5

ClinPred

0.084

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.86

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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