10-26697781-G-A

Variant names:

• chr10-26697781-G-A
• rs1002908038
• NM_014317.5:c.70G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014317.5(PDSS1):​c.70G>A​(p.Gly24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000871 in 1,148,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G24R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: PDSS1 NM_014317.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 0 publications found

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

ENSG00000279212 (HGNC:):

ACMG classification

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=0.1860919).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDSS1	NM_014317.5	MANE Select	c.70G>A	p.Gly24Ser	missense	Exon 1 of 12	NP_055132.2	Q5T2R2-1
	PDSS1	NM_001321978.2		c.70G>A	p.Gly24Ser	missense	Exon 1 of 10	NP_001308907.1	Q5T2R2-2
	PDSS1	NM_001321979.2		c.-524G>A		5_prime_UTR	Exon 1 of 12	NP_001308908.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDSS1	ENST00000376215.10	TSL:1 MANE Select	c.70G>A	p.Gly24Ser	missense	Exon 1 of 12	ENSP00000365388.5	Q5T2R2-1
	PDSS1	ENST00000917009.1		c.70G>A	p.Gly24Ser	missense	Exon 1 of 11	ENSP00000587068.1
	PDSS1	ENST00000869579.1		c.70G>A	p.Gly24Ser	missense	Exon 1 of 10	ENSP00000539638.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.71e-7 AC: 1 AN: 1148652 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 554618

African (AFR) AF: 0.00 AC: 0 AN: 23384

American (AMR) AF: 0.00 AC: 0 AN: 10394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15718

East Asian (EAS) AF: 0.00 AC: 0 AN: 26552

South Asian (SAS) AF: 0.00 AC: 0 AN: 37344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3144

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 961154

Other (OTH) AF: 0.00 AC: 0 AN: 46354

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0090	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.21
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.13
Sift	Benign	0.23	T
Sift4G	Benign	0.74	T
Polyphen		0.016	B
Vest4		0.27
MutPred		0.16		Gain of glycosylation at G24 (P = 0.007)
MVP		0.69
MPC		0.47
ClinPred		0.13	T
GERP RS		1.6
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.077
gMVP		0.19
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1002908038; hg19: chr10-26986710;