rs3734676

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020381.4(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. 14/20 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
NM_020381.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.356

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 138690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-107459275-C-G is described in Lovd as [Benign]. Variant chr6-107459275-C-G is described in Lovd as [Likely_benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDSS2	NM_020381.4 link	c.11G>C	p.Arg4Pro	missense_variant	Exon 1 of 8	ENST00000369037.9	NP_065114.3	Q86YH6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDSS2	ENST00000369037.9 link	c.11G>C	p.Arg4Pro	missense_variant	Exon 1 of 8	1	NM_020381.4	ENSP00000358033.4		Q86YH6-1
PDSS2	ENST00000369031.4 link	c.11G>C	p.Arg4Pro	missense_variant	Exon 1 of 4	1		ENSP00000358027.4		Q86YH6-2

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

GnomAD3 exomes

AF:

0.0155

AC:

3895

AN:

250640

Hom.:

148

AF XY:

0.0144

AC XY:

1958

AN XY:

135672

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 SAS exome

AF:

0.00814

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

Gnomad4 AFR exome

AF:

0.00400

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.00849

Gnomad4 FIN exome

AF:

0.0232

Gnomad4 NFE exome

AF:

0.000720

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.00885

AC:

1347

AN:

152204

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

767

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00513

Gnomad4 AMR

AF:

0.00941

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.00954

Gnomad4 FIN

AF:

0.0231

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.0138

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

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Dec 31, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Kidney disorder

Benign:1

Jun 24, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.094

T;D

Polyphen

0.0

B;B

Vest4

0.12

MPC

1.6

ClinPred

0.063

GERP RS

1.2

Varity_R

0.49

gMVP

0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over