12-121888906-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002813.7(PSMD9):c.50T>C(p.Val17Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,596,832 control chromosomes in the GnomAD database, including 591,063 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.84 ( 54241 hom., cov: 36)

Exomes 𝑓: 0.86 ( 536822 hom. )

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:

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=7.049505E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002813.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMD9	NM_002813.7	MANE Select	c.50T>C	p.Val17Ala	missense	Exon 1 of 6	NP_002804.2
PSMD9	NM_001261400.3		c.50T>C	p.Val17Ala	missense	Exon 1 of 4	NP_001248329.1	O00233-3
PSMD9	NR_048555.3		n.117T>C		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMD9	ENST00000541212.6	TSL:1 MANE Select	c.50T>C	p.Val17Ala	missense	Exon 1 of 6	ENSP00000440485.1	O00233-1
PSMD9	ENST00000537407.5	TSL:1	n.50T>C		non_coding_transcript_exon	Exon 1 of 7	ENSP00000445058.1	O00233-2
ENSG00000256950	ENST00000546333.1	TSL:5	n.50T>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000477146.1	F5H7X1

Frequencies

GnomAD3 genomes

AF:

0.843

AC:

128358

AN:

152184

Hom.:

54201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.834

Gnomad AMI

AF:

0.916

Gnomad AMR

AF:

0.781

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.865

Gnomad SAS

AF:

0.844

Gnomad FIN

AF:

0.772

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.868

Gnomad OTH

AF:

0.851

GnomAD2 exomes

AF:

0.837

AC:

182638

AN:

218164

AF XY:

0.843

show subpopulations

Gnomad AFR exome

AF:

0.834

Gnomad AMR exome

AF:

0.723

Gnomad ASJ exome

AF:

0.906

Gnomad EAS exome

AF:

0.871

Gnomad FIN exome

AF:

0.783

Gnomad NFE exome

AF:

0.869

Gnomad OTH exome

AF:

0.853

GnomAD4 exome

AF:

0.861

AC:

1244096

AN:

1444530

Hom.:

536822

Cov.:

AF XY:

0.862

AC XY:

617851

AN XY:

717118

show subpopulations

African (AFR)

AF:

0.834

AC:

27784

AN:

33302

American (AMR)

AF:

0.728

AC:

30131

AN:

41376

Ashkenazi Jewish (ASJ)

AF:

0.905

AC:

23296

AN:

25750

East Asian (EAS)

AF:

0.851

AC:

33278

AN:

39098

South Asian (SAS)

AF:

0.840

AC:

70372

AN:

83730

European-Finnish (FIN)

AF:

0.780

AC:

40041

AN:

51352

Middle Eastern (MID)

AF:

0.896

AC:

5024

AN:

5610

European-Non Finnish (NFE)

AF:

0.871

AC:

962441

AN:

1104584

Other (OTH)

AF:

0.866

AC:

51729

AN:

59728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

9827

19654

29480

39307

49134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21200

42400

63600

84800

106000

<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:

0.843

AC:

128452

AN:

152302

Hom.:

54241

Cov.:

AF XY:

0.838

AC XY:

62423

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.834

AC:

34660

AN:

41560

American (AMR)

AF:

0.781

AC:

11952

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

3159

AN:

3472

East Asian (EAS)

AF:

0.865

AC:

4481

AN:

5182

South Asian (SAS)

AF:

0.844

AC:

4081

AN:

4834

European-Finnish (FIN)

AF:

0.772

AC:

8182

AN:

10604

Middle Eastern (MID)

AF:

0.912

AC:

268

AN:

294

European-Non Finnish (NFE)

AF:

0.868

AC:

59028

AN:

68022

Other (OTH)

AF:

0.853

AC:

1806

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

1103

2206

3309

4412

5515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.861

Hom.:

189851

Bravo

AF:

0.844

TwinsUK

AF:

0.879

AC:

3260

ALSPAC

AF:

0.880

AC:

3391

ESP6500AA

AF:

0.836

AC:

3675

ESP6500EA

AF:

0.873

AC:

7495

ExAC

AF:

0.825

AC:

98411

Asia WGS

AF:

0.862

AC:

2995

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.51

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0084

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.099

MetaRNN

Benign

7.0e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

PhyloP100

-0.15

PrimateAI

Benign

0.39

PROVEAN

Benign

0.52

REVEL

Benign

0.013

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.018

MPC

0.22

ClinPred

0.0027

GERP RS

-0.45

PromoterAI

0.053

Neutral

(source)

Varity_R

0.016

gMVP

0.14

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over