Genetic Variant NM_002813.7:c.454-437C>T (chr12-121902569-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002813.7(PSMD9):c.454-437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 184,438 control chromosomes in the GnomAD database, including 7,578 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 0.25 ( 5924 hom., cov: 32)

Exomes 𝑓: 0.31 ( 1654 hom. )

Consequence

PSMD9
NM_002813.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0780

Publications

21 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PSMD9	NM_002813.7 link	c.454-437C>T	intron_variant	Intron 3 of 5	ENST00000541212.6	NP_002804.2	O00233-1
PSMD9	NM_001261400.3 link	c.139-437C>T	intron_variant	Intron 1 of 3		NP_001248329.1	O00233-3
PSMD9	NR_048555.3 link	n.309-437C>T	intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD9	ENST00000541212.6 link	c.454-437C>T		intron_variant	Intron 3 of 5	1	NM_002813.7	ENSP00000440485.1		O00233-1
ENSG00000256950	ENST00000546333.1 link	n.242-437C>T		intron_variant	Intron 2 of 3	5		ENSP00000477146.1		F5H7X1

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37837

AN:

151962

Hom.:

5918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.509

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.311

AC:

10070

AN:

32358

Hom.:

1654

Cov.:

AF XY:

0.308

AC XY:

5260

AN XY:

17104

show subpopulations

African (AFR)

AF:

0.0541

AC:

AN:

758

American (AMR)

AF:

0.357

AC:

1029

AN:

2884

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

206

AN:

646

East Asian (EAS)

AF:

0.524

AC:

813

AN:

1552

South Asian (SAS)

AF:

0.318

AC:

1368

AN:

4298

European-Finnish (FIN)

AF:

0.312

AC:

374

AN:

1200

Middle Eastern (MID)

AF:

0.273

AC:

AN:

110

European-Non Finnish (NFE)

AF:

0.296

AC:

5686

AN:

19216

Other (OTH)

AF:

0.309

AC:

523

AN:

1694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

328

657

985

1314

1642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.249

AC:

37850

AN:

152080

Hom.:

5924

Cov.:

AF XY:

0.255

AC XY:

18916

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0626

AC:

2598

AN:

41530

American (AMR)

AF:

0.332

AC:

5063

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

1038

AN:

3470

East Asian (EAS)

AF:

0.509

AC:

2624

AN:

5152

South Asian (SAS)

AF:

0.340

AC:

1639

AN:

4826

European-Finnish (FIN)

AF:

0.331

AC:

3496

AN:

10554

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.300

AC:

20369

AN:

67974

Other (OTH)

AF:

0.273

AC:

576

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1365

2730

4094

5459

6824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.168

Hom.:

403

Bravo

AF:

0.242

Asia WGS

AF:

0.402

AC:

1396

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.93

(source)

DANN

Benign

0.79

PhyloP100

0.078

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over