11-237087-A-G

Variant names:

Variant summary

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

The NM_002817.4(PSMD13):c.38A>G(p.Asn13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,613,486 control chromosomes in the GnomAD database, including 474,032 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.79 ( 48255 hom., cov: 34)

Exomes 𝑓: 0.76 ( 425777 hom. )

Consequence

PSMD13
NM_002817.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46

Publications

56 publications found

Variant links:

Genes affected

PSMD13 (HGNC:9558): (proteasome 26S subunit, non-ATPase 13) 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. Two transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

PSMD13 links:

SIRT3 (HGNC:14931): (sirtuin 3) SIRT3 encodes a member of the sirtuin family of class III histone deacetylases, homologs to the yeast Sir2 protein. The encoded protein is found exclusively in mitochondria, where it can eliminate reactive oxygen species, inhibit apoptosis, and prevent the formation of cancer cells. SIRT3 has far-reaching effects on nuclear gene expression, cancer, cardiovascular disease, neuroprotection, aging, and metabolic control. [provided by RefSeq, May 2019]

SIRT3 links:

ENSG00000298317 (HGNC:):

ENSG00000298317 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 (MetaRNN=7.1342896E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002817.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PSMD13	NM_002817.4	MANE Select	c.38A>G	p.Asn13Ser	missense	Exon 1 of 13	NP_002808.3
PSMD13	NM_175932.3		c.38A>G	p.Asn13Ser	missense	Exon 1 of 11	NP_787128.2
SIRT3	NM_001370321.1		c.-617T>C		upstream_gene	N/A	NP_001357250.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PSMD13	ENST00000532097.6	TSL:1 MANE Select	c.38A>G	p.Asn13Ser	missense	Exon 1 of 13	ENSP00000436186.1
PSMD13	ENST00000382671.8	TSL:1	n.38A>G		non_coding_transcript_exon	Exon 1 of 12	ENSP00000372117.4
PSMD13	ENST00000527047.5	TSL:1	n.84A>G		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.794

AC:

120746

AN:

152166

Hom.:

48204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.884

Gnomad AMI

AF:

0.732

Gnomad AMR

AF:

0.807

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.827

Gnomad SAS

AF:

0.798

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.745

Gnomad OTH

AF:

0.761

GnomAD2 exomes

AF:

0.778

AC:

193409

AN:

248438

AF XY:

0.773

show subpopulations

Gnomad AFR exome

AF:

0.886

Gnomad AMR exome

AF:

0.838

Gnomad ASJ exome

AF:

0.703

Gnomad EAS exome

AF:

0.826

Gnomad FIN exome

AF:

0.763

Gnomad NFE exome

AF:

0.744

Gnomad OTH exome

AF:

0.753

GnomAD4 exome

AF:

0.763

AC:

1114413

AN:

1461202

Hom.:

425777

Cov.:

AF XY:

0.762

AC XY:

553709

AN XY:

726934

show subpopulations

African (AFR)

AF:

0.889

AC:

29733

AN:

33462

American (AMR)

AF:

0.837

AC:

37398

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.696

AC:

18178

AN:

26120

East Asian (EAS)

AF:

0.835

AC:

33151

AN:

39684

South Asian (SAS)

AF:

0.791

AC:

68199

AN:

86228

European-Finnish (FIN)

AF:

0.762

AC:

40665

AN:

53344

Middle Eastern (MID)

AF:

0.691

AC:

3958

AN:

5724

European-Non Finnish (NFE)

AF:

0.753

AC:

837204

AN:

1111592

Other (OTH)

AF:

0.761

AC:

45927

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

13979

27959

41938

55918

69897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20398

40796

61194

81592

101990

<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:

0.794

AC:

120849

AN:

152284

Hom.:

48255

Cov.:

AF XY:

0.796

AC XY:

59286

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.884

AC:

36746

AN:

41578

American (AMR)

AF:

0.808

AC:

12359

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

2395

AN:

3470

East Asian (EAS)

AF:

0.828

AC:

4285

AN:

5178

South Asian (SAS)

AF:

0.798

AC:

3854

AN:

4832

European-Finnish (FIN)

AF:

0.766

AC:

8120

AN:

10600

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.745

AC:

50633

AN:

68004

Other (OTH)

AF:

0.756

AC:

1599

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1317

2634

3951

5268

6585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<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:

0.757

Hom.:

116897

Bravo

AF:

0.802

ESP6500AA

AF:

0.883

AC:

3892

ESP6500EA

AF:

0.744

AC:

6398

ExAC

AF:

0.777

AC:

94334

Asia WGS

AF:

0.807

AC:

2807

AN:

3478

EpiCase

AF:

0.738

EpiControl

AF:

0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0014

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.19

MetaRNN

Benign

7.1e-7

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.6

PhyloP100

3.5

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.21

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.081

MPC

0.27

ClinPred

0.0041

GERP RS

4.1

PromoterAI

0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.054

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