12-121894821-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002813.7(PSMD9):c.221C>T(p.Thr74Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00115 in 1,613,654 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

PSMD9
NM_002813.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.33

Publications

8 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008055031).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00129 (197/152276) while in subpopulation EAS AF = 0.0359 (186/5184). AF 95% confidence interval is 0.0317. There are 5 homozygotes in GnomAd4. There are 106 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD9	NM_002813.7 link	c.221C>T	p.Thr74Ile	missense_variant	Exon 2 of 6	ENST00000541212.6	NP_002804.2	O00233-1
PSMD9	NR_048555.3 link	n.288C>T		non_coding_transcript_exon_variant	Exon 2 of 5
PSMD9	NM_001261400.3 link	c.138+5827C>T		intron_variant	Intron 1 of 3		NP_001248329.1	O00233-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD9	ENST00000541212.6 link	c.221C>T	p.Thr74Ile	missense_variant	Exon 2 of 6	1	NM_002813.7	ENSP00000440485.1		O00233-1
ENSG00000256950	ENST00000546333.1 link	n.221C>T		non_coding_transcript_exon_variant	Exon 2 of 4	5		ENSP00000477146.1		F5H7X1

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

196

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0356

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00276

AC:

689

AN:

249290

AF XY:

0.00258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0356

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000989

GnomAD4 exome

AF:

0.00114

AC:

1660

AN:

1461378

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

820

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.0000896

AC:

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.0370

AC:

1469

AN:

39686

South Asian (SAS)

AF:

0.000964

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111806

Other (OTH)

AF:

0.00149

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

171

256

342

427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152276

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41570

American (AMR)

AF:

0.000196

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0359

AC:

186

AN:

5184

South Asian (SAS)

AF:

0.000623

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000207

Hom.:

Bravo

AF:

0.00175

ExAC

AF:

0.00265

AC:

322

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.0081

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

M;.;.

PhyloP100

5.3

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.18

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.24

B;.;.

Vest4

0.76

MVP

0.40

MPC

0.25

ClinPred

0.086

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.51

Mutation Taster

=71/29

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over