rs3734675

Variant summary

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

The NM_020381.4(PDSS2):c.7T>C(p.Phe3Leu) 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 1,613,980 control chromosomes in the GnomAD database, including 329 homozygotes. 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 0.0088 ( 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: 2.17

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=0.0016657114).

BP6

Variant 6-107459279-A-G is Benign according to our data. Variant chr6-107459279-A-G is described in ClinVar as [Benign]. Clinvar id is 138689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-107459279-A-G is described in Lovd as [Benign]. Variant chr6-107459279-A-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/exons	MANE	UniProt
PDSS2	NM_020381.4 linkuse as main transcript	c.7T>C	p.Phe3Leu	missense_variant	1/8	ENST00000369037.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDSS2	ENST00000369037.9 linkuse as main transcript	c.7T>C	p.Phe3Leu	missense_variant	1/8	1	NM_020381.4	P1	Q86YH6-1
PDSS2	ENST00000369031.4 linkuse as main transcript	c.7T>C	p.Phe3Leu	missense_variant	1/4	1			Q86YH6-2

Frequencies

GnomAD3 genomes

AF:

0.00880

AC:

1339

AN:

152188

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:

0.000985

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0155

AC:

3895

AN:

250590

Hom.:

147

AF XY:

0.0144

AC XY:

1957

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.00478

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:

8414

AN:

1461672

Hom.:

282

Cov.:

AF XY:

0.00571

AC XY:

4152

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

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:

0.000719

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.00884

AC:

1347

AN:

152308

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

768

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00512

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:

0.000985

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00606

Hom.:

Bravo

AF:

0.00910

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00140

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

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Jun 14, 2017	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Kidney disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jun 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Benign

0.72

DEOGEN2

Benign

0.060

T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.27

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.94

N;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.042

MutPred

0.11

Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);

MPC

1.3

ClinPred

0.045

GERP RS

4.0

Varity_R

0.065

gMVP

0.40

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

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