10-26697764-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014317.5(PDSS1):c.53C>T(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000879 in 1,138,088 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A18G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.8e-7 ( 0 hom. )

Consequence

PDSS1
NM_014317.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0180

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=0.23795182).

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.53C>T	p.Ala18Val	missense	Exon 1 of 12	NP_055132.2	Q5T2R2-1
PDSS1	NM_001321978.2		c.53C>T	p.Ala18Val	missense	Exon 1 of 10	NP_001308907.1	Q5T2R2-2
PDSS1	NM_001321979.2		c.-541C>T		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.53C>T	p.Ala18Val	missense	Exon 1 of 12	ENSP00000365388.5	Q5T2R2-1
PDSS1	ENST00000917009.1		c.53C>T	p.Ala18Val	missense	Exon 1 of 11	ENSP00000587068.1
PDSS1	ENST00000869579.1		c.53C>T	p.Ala18Val	missense	Exon 1 of 10	ENSP00000539638.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.79e-7

AC:

AN:

1138088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

548612

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000433

AC:

AN:

23106

American (AMR)

AF:

0.00

AC:

AN:

9172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15062

East Asian (EAS)

AF:

0.00

AC:

AN:

26548

South Asian (SAS)

AF:

0.00

AC:

AN:

34794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3062

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

956494

Other (OTH)

AF:

0.00

AC:

AN:

45780

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.8

PhyloP100

-0.018

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.010

REVEL

Benign

0.20

Sift

Benign

0.18

Sift4G

Benign

0.10

Polyphen

0.22

Vest4

0.16

MutPred

0.17

Loss of methylation at R19 (P = 0.0766)

MVP

0.74

MPC

0.47

ClinPred

0.29

GERP RS

3.8

PromoterAI

0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.036

gMVP

0.24

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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