NM_002814.4:c.677G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002814.4(PSMD10):c.677G>A(p.Gly226Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,198,446 control chromosomes in the GnomAD database, including 4 homozygotes. There are 145 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00075 ( 2 hom., 29 hem., cov: 24)

Exomes 𝑓: 0.00039 ( 2 hom. 116 hem. )

Consequence

PSMD10
NM_002814.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.36

Publications

1 publications found

Variant links:

Genes affected

PSMD10 (HGNC:9555): (proteasome 26S subunit, non-ATPase 10) This gene encodes a subunit of the PA700/19S complex, which is the regulatory component of the 26S proteasome. The 26S proteosome complex is required for ubiquitin-dependent protein degradation. This protein is a non-ATPase subunit that may be involved in protein-protein interactions. Aberrant expression of this gene may paly a role in tumorigenesis. Two transcripts encoding different isoforms have been described. Pseudogenes have been identified on chromosomes 3 and 20.[provided by RefSeq, Mar 2011]

PSMD10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038719177).

BP6

Variant X-108084978-C-T is Benign according to our data. Variant chrX-108084978-C-T is described in ClinVar as Benign. ClinVar VariationId is 726032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00075 (84/111972) while in subpopulation EAS AF = 0.0218 (78/3571). AF 95% confidence interval is 0.0179. There are 2 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002814.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD10	NM_002814.4	MANE Select	c.677G>A	p.Gly226Asp	missense	Exon 5 of 5	NP_002805.1	O75832-1
	PSMD10	NM_170750.3		c.*142G>A		3_prime_UTR	Exon 5 of 5	NP_736606.1	O75832-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMD10	ENST00000217958.8	TSL:1 MANE Select	c.677G>A	p.Gly226Asp	missense	Exon 5 of 5	ENSP00000217958.3	O75832-1
PSMD10	ENST00000361815.9	TSL:1	c.*142G>A		3_prime_UTR	Exon 5 of 5	ENSP00000354906.5	O75832-2
PSMD10	ENST00000923416.1		c.677G>A	p.Gly226Asp	missense	Exon 5 of 5	ENSP00000593475.1

Frequencies

GnomAD3 genomes

AF:

0.000751

AC:

AN:

111918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000650

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000378

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0218

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00217

AC:

361

AN:

166231

AF XY:

0.00174

show subpopulations

Gnomad AFR exome

AF:

0.0000800

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0277

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.000391

AC:

425

AN:

1086474

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

116

AN XY:

354202

show subpopulations

African (AFR)

AF:

0.0000388

AC:

AN:

25785

American (AMR)

AF:

0.000119

AC:

AN:

33688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18822

East Asian (EAS)

AF:

0.0121

AC:

360

AN:

29744

South Asian (SAS)

AF:

0.0000583

AC:

AN:

51459

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40239

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4058

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

837123

Other (OTH)

AF:

0.00105

AC:

AN:

45556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000750

AC:

AN:

111972

Hom.:

Cov.:

AF XY:

0.000848

AC XY:

AN XY:

34178

show subpopulations

African (AFR)

AF:

0.0000649

AC:

AN:

30816

American (AMR)

AF:

0.000378

AC:

AN:

10585

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.0218

AC:

AN:

3571

South Asian (SAS)

AF:

0.00

AC:

AN:

2687

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53142

Other (OTH)

AF:

0.00

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000268

Hom.:

Bravo

AF:

0.000842

ExAC

AF:

0.00185

AC:

225

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.88

PhyloP100

2.4

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.52

REVEL

Benign

0.070

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.11

MVP

0.81

MPC

1.3

ClinPred

0.037

GERP RS

2.1

Varity_R

0.48

gMVP

0.63

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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