rs319053

Positions:

• chr6-107403954-A-G

Variant summary

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

The NM_020381.4(PDSS2):​c.296+55036T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 152,362 control chromosomes in the GnomAD database, including 75,365 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 0.99 (75365 hom., cov: 33)
• Consequence: PDSS2 NM_020381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDSS2	NM_020381.4	c.296+55036T>C		intron_variant		ENST00000369037.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDSS2	ENST00000369037.9	c.296+55036T>C		intron_variant		1	NM_020381.4	P1
PDSS2	ENST00000369031.4	c.296+55036T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.995 AC: 151414 AN: 152244 Hom.: 75304 Cov.: 33

Gnomad AFR AF: 0.999

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.989

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.997

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

GnomAD4 genome AF: 0.995 AC: 151534 AN: 152362 Hom.: 75365 Cov.: 33 AF XY: 0.994 AC XY: 74076 AN XY: 74508

Gnomad4 AFR AF: 0.999

Gnomad4 AMR AF: 0.998

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.989

Gnomad4 NFE AF: 0.994

Gnomad4 OTH AF: 0.997

Alfa AF: 0.995 Hom.: 9345

Bravo AF: 0.995

Asia WGS AF: 0.985 AC: 3427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.7
DANN	Benign	0.52

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: rs319053; hg19: chr6-107725158;