chr10-26697780-C-T

Variant names:

• chr10-26697780-C-T
• rs905436294
• NM_014317.5:c.69C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001321979.2(PDSS1):​c.-525C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,299,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: PDSS1 NM_001321979.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.34
• 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_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 10-26697780-C-T is Benign according to our data. Variant chr10-26697780-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2991307.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321979.2. 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.69C>T	p.Pro23Pro	synonymous	Exon 1 of 12	NP_055132.2	Q5T2R2-1
	PDSS1	NM_001321979.2		c.-525C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001308908.1
	PDSS1	NM_001321978.2		c.69C>T	p.Pro23Pro	synonymous	Exon 1 of 10	NP_001308907.1	Q5T2R2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDSS1	ENST00000376215.10	TSL:1 MANE Select	c.69C>T	p.Pro23Pro	synonymous	Exon 1 of 12	ENSP00000365388.5	Q5T2R2-1
	PDSS1	ENST00000917009.1		c.69C>T	p.Pro23Pro	synonymous	Exon 1 of 11	ENSP00000587068.1
	PDSS1	ENST00000869579.1		c.69C>T	p.Pro23Pro	synonymous	Exon 1 of 10	ENSP00000539638.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151926 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000941 AC: 1 AN: 10626 AF XY: 0.000156

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000233

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000218 AC: 25 AN: 1147178 Hom.: 0 Cov.: 30 AF XY: 0.0000307 AC XY: 17 AN XY: 553744

African (AFR) AF: 0.00 AC: 0 AN: 23356

American (AMR) AF: 0.00 AC: 0 AN: 10260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15632

East Asian (EAS) AF: 0.00 AC: 0 AN: 26550

South Asian (SAS) AF: 0.00 AC: 0 AN: 37064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3132

European-Non Finnish (NFE) AF: 0.0000250 AC: 24 AN: 960430

Other (OTH) AF: 0.0000216 AC: 1 AN: 46240

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151926 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74194

African (AFR) AF: 0.0000724 AC: 3 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.6
DANN	Benign	0.88
PhyloP100		-1.3
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs905436294; hg19: chr10-26986709;