10-26697758-C-G

Variant names:

• chr10-26697758-C-G
• NM_014317.5:c.47C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014317.5(PDSS1):​c.47C>G​(p.Pro16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000878 in 1,139,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: PDSS1 NM_014317.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.261

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]

ENSG00000279212 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2943452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDSS1	NM_014317.5	c.47C>G	p.Pro16Arg	missense_variant	Exon 1 of 12	ENST00000376215.10	NP_055132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDSS1	ENST00000376215.10	c.47C>G	p.Pro16Arg	missense_variant	Exon 1 of 12	1	NM_014317.5	ENSP00000365388.5
ENSG00000279212	ENST00000623958.1	n.-133G>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.78e-7 AC: 1 AN: 1139422 Hom.: 0 Cov.: 30 AF XY: 0.00000182 AC XY: 1 AN XY: 549504

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000285

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jan 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47C>G (p.P16R) alteration is located in exon 1 (coding exon 1) of the PDSS1 gene. This alteration results from a C to G substitution at nucleotide position 47, causing the proline (P) at amino acid position 16 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.8	L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.22
Sift	Uncertain	0.015	D
Sift4G	Benign	0.76	T
Polyphen		0.015	B
Vest4		0.35
MutPred		0.23		Gain of MoRF binding (P = 0.0295);
MVP		0.73
MPC		0.52
ClinPred		0.26	T
GERP RS		3.8
Varity_R		0.14
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-26986687;