dbSNP rs2230681: PSMD9:p.Val17Asp (chr12-121888906-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002813.7(PSMD9):c.50T>A(p.Val17Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 36)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PSMD9
NM_002813.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.148

Publications

48 publications found

Variant links:

Genes affected

PSMD9 (HGNC:9567): (proteasome 26S subunit, non-ATPase 9) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2012]

PSMD9 links:

ENSG00000256950 (HGNC:):

ENSG00000256950 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055524558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PSMD9	NM_002813.7 link	c.50T>A	p.Val17Asp	missense_variant	Exon 1 of 6	ENST00000541212.6	NP_002804.2
PSMD9	NM_001261400.3 link	c.50T>A	p.Val17Asp	missense_variant	Exon 1 of 4		NP_001248329.1
PSMD9	NR_048555.3 link	n.117T>A		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD9	ENST00000541212.6 link	c.50T>A	p.Val17Asp	missense_variant	Exon 1 of 6	1	NM_002813.7	ENSP00000440485.1
ENSG00000256950	ENST00000546333.1 link	n.50T>A		non_coding_transcript_exon_variant	Exon 1 of 4	5		ENSP00000477146.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1444668

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717186

African (AFR)

AF:

0.00

AC:

AN:

33302

American (AMR)

AF:

0.00

AC:

AN:

41412

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25750

East Asian (EAS)

AF:

0.00

AC:

AN:

39108

South Asian (SAS)

AF:

0.00

AC:

AN:

83744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104642

Other (OTH)

AF:

0.00

AC:

AN:

59732

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.2

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0084

T;T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.51

T;T;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.056

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;.;.;N

PhyloP100

-0.15

PrimateAI

Benign

0.42

PROVEAN

Benign

0.090

N;N;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.017

D;D;D;T

Sift4G

Benign

0.55

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.080

MutPred

0.32

Gain of catalytic residue at V18 (P = 0.0038);Gain of catalytic residue at V18 (P = 0.0038);Gain of catalytic residue at V18 (P = 0.0038);Gain of catalytic residue at V18 (P = 0.0038);

MVP

0.067

MPC

0.30

ClinPred

0.083

GERP RS

-0.45

PromoterAI

0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.24

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over