10-26697781-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting

The NM_014317.5(PDSS1):c.70G>C(p.Gly24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000646 in 1,300,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

PDSS1
NM_014317.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 0.211

Publications

0 publications found

Variant links:

Genes affected

PDSS1 (HGNC:17759): (decaprenyl diphosphate synthase subunit 1) The protein encoded by this gene is an enzyme that elongates 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. The protein may be peripherally associated with the inner mitochondrial membrane, though no transit peptide has been definitively identified to date. Defects in this gene are a cause of coenzyme Q10 deficiency. [provided by RefSeq, Jul 2008]

PDSS1 Gene-Disease associations (from GenCC):

deafness-encephaloneuropathy-obesity-valvulopathy syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
mitochondrial disease
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

PDSS1 links:

ENSG00000279212 (HGNC:):

ENSG00000279212 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2707129).

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0000705 (81/1148652) while in subpopulation NFE AF = 0.0000812 (78/961154). AF 95% confidence interval is 0.0000661. There are 0 homozygotes in GnomAdExome4. There are 41 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014317.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDSS1	NM_014317.5	MANE Select	c.70G>C	p.Gly24Arg	missense	Exon 1 of 12	NP_055132.2	Q5T2R2-1
PDSS1	NM_001321978.2		c.70G>C	p.Gly24Arg	missense	Exon 1 of 10	NP_001308907.1	Q5T2R2-2
PDSS1	NM_001321979.2		c.-524G>C		5_prime_UTR	Exon 1 of 12	NP_001308908.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDSS1	ENST00000376215.10	TSL:1 MANE Select	c.70G>C	p.Gly24Arg	missense	Exon 1 of 12	ENSP00000365388.5	Q5T2R2-1
PDSS1	ENST00000917009.1		c.70G>C	p.Gly24Arg	missense	Exon 1 of 11	ENSP00000587068.1
PDSS1	ENST00000869579.1		c.70G>C	p.Gly24Arg	missense	Exon 1 of 10	ENSP00000539638.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

11234

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000705

AC:

AN:

1148652

Hom.:

Cov.:

AF XY:

0.0000739

AC XY:

AN XY:

554618

show subpopulations

African (AFR)

AF:

0.0000428

AC:

AN:

23384

American (AMR)

AF:

0.00

AC:

AN:

10394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15718

East Asian (EAS)

AF:

0.00

AC:

AN:

26552

South Asian (SAS)

AF:

0.00

AC:

AN:

37344

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3144

European-Non Finnish (NFE)

AF:

0.0000812

AC:

AN:

961154

Other (OTH)

AF:

0.0000431

AC:

AN:

46354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41530

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67964

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deafness-encephaloneuropathy-obesity-valvulopathy syndrome (1)

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.085

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.2

PhyloP100

0.21

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.18

REVEL

Benign

0.20

Sift

Benign

0.040

Sift4G

Benign

0.38

Polyphen

0.66

Vest4

0.20

MutPred

0.24

Gain of methylation at G24 (P = 0.0106)

MVP

0.76

MPC

0.60

ClinPred

0.56

GERP RS

1.6

PromoterAI

0.00020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.061

gMVP

0.23

Mutation Taster

=91/9

polymorphism

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over