rs319053

Variant names:

• chr6-107403954-A-G
• rs319053
• NM_020381.4:c.296+55036T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

PDSS2 Gene-Disease associations (from GenCC):

• coenzyme Q10 deficiency, primary, 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome with nephrotic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PDSS2	NM_020381.4	c.296+55036T>C		intron_variant	Intron 1 of 7	ENST00000369037.9	NP_065114.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDSS2	ENST00000369037.9	c.296+55036T>C		intron_variant	Intron 1 of 7	1	NM_020381.4	ENSP00000358033.4
PDSS2	ENST00000369031.4	c.296+55036T>C		intron_variant	Intron 1 of 3	1		ENSP00000358027.4

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

African (AFR) AF: 0.999 AC: 41546 AN: 41586

American (AMR) AF: 0.998 AC: 15285 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3430 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4997 AN: 5178

South Asian (SAS) AF: 0.999 AC: 4817 AN: 4824

European-Finnish (FIN) AF: 0.989 AC: 10510 AN: 10626

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67660 AN: 68046

Other (OTH) AF: 0.997 AC: 2108 AN: 2114

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
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs319053; hg19: chr6-107725158;