Genetic Variant PDSS1:p.Cys12Arg (chr10-26697745-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014317.5(PDSS1):c.34T>C(p.Cys12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C12G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDSS1
NM_014317.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00600

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40189368).

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.34T>C	p.Cys12Arg	missense	Exon 1 of 12	NP_055132.2	Q5T2R2-1
PDSS1	NM_001321978.2		c.34T>C	p.Cys12Arg	missense	Exon 1 of 10	NP_001308907.1	Q5T2R2-2
PDSS1	NM_001321979.2		c.-560T>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.34T>C	p.Cys12Arg	missense	Exon 1 of 12	ENSP00000365388.5	Q5T2R2-1
PDSS1	ENST00000917009.1		c.34T>C	p.Cys12Arg	missense	Exon 1 of 11	ENSP00000587068.1
PDSS1	ENST00000869579.1		c.34T>C	p.Cys12Arg	missense	Exon 1 of 10	ENSP00000539638.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1143244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

551868

African (AFR)

AF:

0.00

AC:

AN:

23176

American (AMR)

AF:

0.00

AC:

AN:

9656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15436

East Asian (EAS)

AF:

0.00

AC:

AN:

26532

South Asian (SAS)

AF:

0.00

AC:

AN:

36498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3086

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

958434

Other (OTH)

AF:

0.00

AC:

AN:

45964

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.046

Eigen_PC

Benign

-0.078

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.51

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.29

MutationAssessor

Benign

2.0

PhyloP100

0.0060

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0070

Polyphen

0.84

Vest4

0.38

MutPred

0.30

Gain of helix (P = 0.0199)

MVP

0.82

MPC

1.7

ClinPred

0.97

GERP RS

3.2

PromoterAI

0.058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.91

gMVP

0.41

Mutation Taster

=75/25

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over