Genetic Variant PSMD10:p.Gly226Asp (chrX-108084978-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002814.4(PSMD10):c.677G>A(p.Gly226Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,198,446 control chromosomes in the GnomAD database, including 4 homozygotes. There are 145 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00075 ( 2 hom., 29 hem., cov: 24)

Exomes 𝑓: 0.00039 ( 2 hom. 116 hem. )

Consequence

PSMD10
NM_002814.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.36

Variant links:

Genes affected

PSMD10 (HGNC:9555): (proteasome 26S subunit, non-ATPase 10) This gene encodes a subunit of the PA700/19S complex, which is the regulatory component of the 26S proteasome. The 26S proteosome complex is required for ubiquitin-dependent protein degradation. This protein is a non-ATPase subunit that may be involved in protein-protein interactions. Aberrant expression of this gene may paly a role in tumorigenesis. Two transcripts encoding different isoforms have been described. Pseudogenes have been identified on chromosomes 3 and 20.[provided by RefSeq, Mar 2011]

PSMD10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038719177).

BP6

Variant X-108084978-C-T is Benign according to our data. Variant chrX-108084978-C-T is described in ClinVar as [Benign]. Clinvar id is 726032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00075 (84/111972) while in subpopulation EAS AF= 0.0218 (78/3571). AF 95% confidence interval is 0.0179. There are 2 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD10	NM_002814.4 link	c.677G>A	p.Gly226Asp	missense_variant	Exon 5 of 5	ENST00000217958.8	NP_002805.1	O75832-1
PSMD10	NM_170750.3 link	c.*142G>A		3_prime_UTR_variant	Exon 5 of 5		NP_736606.1	O75832-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD10	ENST00000217958.8 link	c.677G>A	p.Gly226Asp	missense_variant	Exon 5 of 5	1	NM_002814.4	ENSP00000217958.3		O75832-1

Frequencies

GnomAD3 genomes

AF:

0.000751

AC:

AN:

111918

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

AN XY:

34114

show subpopulations

Gnomad AFR

AF:

0.0000650

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000378

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0218

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

GnomAD3 exomes

AF:

0.00217

AC:

361

AN:

166231

Hom.:

AF XY:

0.00174

AC XY:

AN XY:

52757

show subpopulations

Gnomad AFR exome

AF:

0.0000800

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0277

Gnomad SAS exome

AF:

0.000268

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.000391

AC:

425

AN:

1086474

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

116

AN XY:

354202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000388

Gnomad4 AMR exome

AF:

0.000119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0121

Gnomad4 SAS exome

AF:

0.0000583

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000750

AC:

AN:

111972

Hom.:

Cov.:

AF XY:

0.000848

AC XY:

AN XY:

34178

show subpopulations

Gnomad4 AFR

AF:

0.0000649

Gnomad4 AMR

AF:

0.000378

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0218

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000332

Hom.:

Bravo

AF:

0.000842

ExAC

AF:

0.00185

AC:

225

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

T;.;.

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

D;D;D

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.88

L;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.52

N;N;N

REVEL

Benign

0.070

Sift

Uncertain

0.0040

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.0

B;.;.

Vest4

0.11

MVP

0.81

MPC

1.3

ClinPred

0.037

GERP RS

2.1

Varity_R

0.48

gMVP

0.63

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