NM_020381.4:c.7T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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
NM_020381.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.17

Publications

10 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=0.0016657114).

BP6

Variant 6-107459279-A-G is Benign according to our data. Variant chr6-107459279-A-G is described in CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar as Benign. Clinvar id is 138689.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDSS2	NM_020381.4 link	c.7T>C	p.Phe3Leu	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.7T>C	p.Phe3Leu	missense_variant	Exon 1 of 8	1	NM_020381.4	ENSP00000358033.4		Q86YH6-1
PDSS2	ENST00000369031.4 link	c.7T>C	p.Phe3Leu	missense_variant	Exon 1 of 4	1		ENSP00000358027.4		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

GnomAD2 exomes

AF:

0.0155

AC:

3895

AN:

250590

AF XY:

0.0144

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 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

African (AFR)

AF:

0.00397

AC:

133

AN:

33474

American (AMR)

AF:

0.0165

AC:

739

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26134

East Asian (EAS)

AF:

0.103

AC:

4093

AN:

39696

South Asian (SAS)

AF:

0.00849

AC:

732

AN:

86252

European-Finnish (FIN)

AF:

0.0232

AC:

1234

AN:

53258

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000719

AC:

799

AN:

1111984

Other (OTH)

AF:

0.0111

AC:

672

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

423

846

1269

1692

2115

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:

0.00884

AC:

1347

AN:

152308

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

768

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00512

AC:

213

AN:

41580

American (AMR)

AF:

0.00941

AC:

144

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.116

AC:

603

AN:

5178

South Asian (SAS)

AF:

0.00954

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0231

AC:

245

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000985

AC:

AN:

68014

Other (OTH)

AF:

0.0137

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

129

193

258

322

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:

0.00620

Hom.:

107

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

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

- -

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. -

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

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

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

PhyloP100

2.2

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

PromoterAI

0.072

Neutral

(source)

Varity_R

0.065

gMVP

0.40

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over