rs319123

Positions:

• chr6-107399791-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020381.4(PDSS2):​c.296+59199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,800 control chromosomes in the GnomAD database, including 16,552 homozygotes. 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: 𝑓 0.45 (16552 hom., cov: 31)
• Consequence: PDSS2 NM_020381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

Genes affected

PDSS2 (HGNC:23041): (decaprenyl diphosphate synthase subunit 2) The protein encoded by this gene is an enzyme that synthesizes 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. Defects in this gene are a cause of coenzyme Q10 deficiency.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDSS2	NM_020381.4	c.296+59199G>A		intron_variant		ENST00000369037.9	NP_065114.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDSS2	ENST00000369037.9	c.296+59199G>A		intron_variant		1	NM_020381.4	ENSP00000358033.4
PDSS2	ENST00000369031.4	c.296+59199G>A		intron_variant		1		ENSP00000358027.4

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68866 AN: 151686 Hom.: 16538 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.454 AC: 68909 AN: 151800 Hom.: 16552 Cov.: 31 AF XY: 0.445 AC XY: 32986 AN XY: 74180

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.505

Alfa AF: 0.483 Hom.: 3186

Bravo AF: 0.449

Asia WGS AF: 0.232 AC: 809 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.37

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

LitVar

Other links and lift over

dbSNP: rs319123; hg19: chr6-107720995;