Genetic Variant PSMD6:p.Asn2Asp (chr3-64023832-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000394431.6(PSMD6):c.4A>G(p.Asn2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,467,414 control chromosomes in the GnomAD database, including 40,228 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 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 0.23 ( 4058 hom., cov: 33)

Exomes 𝑓: 0.23 ( 36170 hom. )

Consequence

PSMD6
ENST00000394431.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.164

Publications

17 publications found

Variant links:

Genes affected

PSMD6 (HGNC:9564): (proteasome 26S subunit, non-ATPase 6) This gene encodes a member of the protease subunit S10 family. The encoded protein is a subunit of the 26S proteasome which colocalizes with DNA damage foci and is involved in the ATP-dependent degradation of ubiquinated proteins. Alternative splicing results in multiple transcript variants [provided by RefSeq, Nov 2012]

PSMD6 links:

LOC105377121 (HGNC:):

LOC105377121 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=2.2879243E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD6	NM_001271780.2 link	c.4A>G	p.Asn2Asp	missense_variant	Exon 1 of 8		NP_001258709.1	Q15008-2
LOC105377121	XR_940906.3 link	n.-243T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD6	ENST00000394431.6 link	c.4A>G	p.Asn2Asp	missense_variant	Exon 1 of 8	1		ENSP00000377952.2		Q15008-2

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34302

AN:

152094

Hom.:

4056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.216

AC:

29222

AN:

135332

AF XY:

0.221

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.0960

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.252

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.230

AC:

302742

AN:

1315202

Hom.:

36170

Cov.:

AF XY:

0.231

AC XY:

150532

AN XY:

651710

show subpopulations

African (AFR)

AF:

0.211

AC:

6326

AN:

29982

American (AMR)

AF:

0.103

AC:

3658

AN:

35408

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

4759

AN:

24736

East Asian (EAS)

AF:

0.404

AC:

14236

AN:

35242

South Asian (SAS)

AF:

0.228

AC:

17611

AN:

77172

European-Finnish (FIN)

AF:

0.255

AC:

8610

AN:

33808

Middle Eastern (MID)

AF:

0.186

AC:

1038

AN:

5566

European-Non Finnish (NFE)

AF:

0.229

AC:

233318

AN:

1017662

Other (OTH)

AF:

0.237

AC:

13186

AN:

55626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

10372

20744

31117

41489

51861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7934

15868

23802

31736

39670

<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:

0.225

AC:

34305

AN:

152212

Hom.:

4058

Cov.:

AF XY:

0.227

AC XY:

16869

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.213

AC:

8866

AN:

41536

American (AMR)

AF:

0.148

AC:

2269

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

660

AN:

3472

East Asian (EAS)

AF:

0.421

AC:

2178

AN:

5172

South Asian (SAS)

AF:

0.236

AC:

1140

AN:

4828

European-Finnish (FIN)

AF:

0.262

AC:

2771

AN:

10574

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.231

AC:

15728

AN:

68016

Other (OTH)

AF:

0.211

AC:

447

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1385

2769

4154

5538

6923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.222

Hom.:

9158

Bravo

AF:

0.216

TwinsUK

AF:

0.234

AC:

869

ALSPAC

AF:

0.245

AC:

946

ExAC

AF:

0.205

AC:

3629

Asia WGS

AF:

0.339

AC:

1174

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.3

(source)

DANN

Benign

0.43

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.17

MetaRNN

Benign

0.00023

MetaSVM

Benign

-0.94

PhyloP100

-0.16

PROVEAN

Benign

0.70

REVEL

Benign

0.051

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.029

ClinPred

0.032

GERP RS

1.2

PromoterAI

-0.0062

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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