NM_014317.5:c.52dupG

Variant names:

• chr10-26697761-C-CG
• NM_014317.5:c.52dupG

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_014317.5(PDSS1):​c.52dupG​(p.Ala18GlyfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDSS1 NM_014317.5 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.418
• 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: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 15 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-26697761-C-CG is Pathogenic according to our data. Variant chr10-26697761-C-CG is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3594203.Status of the report is criteria_provided_single_submitter, 1 stars.

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.52dupG	p.Ala18GlyfsTer29	frameshift	Exon 1 of 12	NP_055132.2	Q5T2R2-1
	PDSS1	NM_001321978.2		c.52dupG	p.Ala18GlyfsTer29	frameshift	Exon 1 of 10	NP_001308907.1	Q5T2R2-2
	PDSS1	NM_001321979.2		c.-542dupG		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.52dupG	p.Ala18GlyfsTer29	frameshift	Exon 1 of 12	ENSP00000365388.5	Q5T2R2-1
	PDSS1	ENST00000917009.1		c.52dupG	p.Ala18GlyfsTer29	frameshift	Exon 1 of 11	ENSP00000587068.1
	PDSS1	ENST00000869579.1		c.52dupG	p.Ala18GlyfsTer29	frameshift	Exon 1 of 10	ENSP00000539638.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Deafness-encephaloneuropathy-obesity-valvulopathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.42

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

hg19: chr10-26986690;