rs3734676

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000369037.9(PDSS2):c.11G>C(p.Arg4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 1,613,900 control chromosomes in the GnomAD database, including 329 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 282 hom. )

Consequence

PDSS2
ENST00000369037.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.356

Publications

6 publications found

Variant links:

Genes affected

PDSS2 (HGNC:23041): (decaprenyl diphosphate synthase subunit 2) The protein encoded by this gene is an enzyme that synthesizes the prenyl side-chain of coenzyme Q, or ubiquinone, one of the key elements in the respiratory chain. The gene product catalyzes the formation of all trans-polyprenyl pyrophosphates from isopentyl diphosphate in the assembly of polyisoprenoid side chains, the first step in coenzyme Q biosynthesis. Defects in this gene are a cause of coenzyme Q10 deficiency.[provided by RefSeq, Oct 2009]

PDSS2 Gene-Disease associations (from GenCC):

coenzyme Q10 deficiency, primary, 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
Leigh syndrome with nephrotic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PDSS2 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=0.0021348894).

BP6

Variant 6-107459275-C-G is Benign according to our data. Variant chr6-107459275-C-G is described in ClinVar as Benign. ClinVar VariationId is 138690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369037.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDSS2	NM_020381.4	MANE Select	c.11G>C	p.Arg4Pro	missense	Exon 1 of 8	NP_065114.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDSS2	ENST00000369037.9	TSL:1 MANE Select	c.11G>C	p.Arg4Pro	missense	Exon 1 of 8	ENSP00000358033.4
	PDSS2	ENST00000369031.4	TSL:1	c.11G>C	p.Arg4Pro	missense	Exon 1 of 4	ENSP00000358027.4

Frequencies

GnomAD3 genomes

AF:

0.00880

AC:

1339

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00502

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00923

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.00953

Gnomad FIN

AF:

0.0231

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.0155

AC:

3895

AN:

250640

AF XY:

0.0144

show subpopulations

Gnomad AFR exome

AF:

0.00483

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.00947

GnomAD4 exome

AF:

0.00576

AC:

8418

AN:

1461696

Hom.:

282

Cov.:

AF XY:

0.00571

AC XY:

4155

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.00400

AC:

134

AN:

33476

American (AMR)

AF:

0.0165

AC:

740

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26136

East Asian (EAS)

AF:

0.103

AC:

4092

AN:

39694

South Asian (SAS)

AF:

0.00849

AC:

732

AN:

86238

European-Finnish (FIN)

AF:

0.0232

AC:

1234

AN:

53284

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000720

AC:

801

AN:

1111994

Other (OTH)

AF:

0.0111

AC:

673

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

432

864

1295

1727

2159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<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:

0.00885

AC:

1347

AN:

152204

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

767

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00513

AC:

213

AN:

41534

American (AMR)

AF:

0.00941

AC:

144

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.116

AC:

602

AN:

5170

South Asian (SAS)

AF:

0.00954

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0231

AC:

245

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00100

AC:

AN:

68010

Other (OTH)

AF:

0.0138

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

123

184

246

307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.00911

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.0143

AC:

1741

Asia WGS

AF:

0.0610

AC:

210

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Kidney disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

-0.36

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.96

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Benign

0.094

Polyphen

0.0

Vest4

0.12

MPC

1.6

ClinPred

0.063

GERP RS

1.2

PromoterAI

-0.021

Neutral

(source)

Varity_R

0.49

gMVP

0.76

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over