6-107194186-C-T

Variant names:

• chr6-107194186-C-T
• rs3734679
• NM_020381.4:c.1009-332G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020381.4(PDSS2):​c.1009-332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,086 control chromosomes in the GnomAD database, including 5,130 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 0.23 (5130 hom., cov: 32)
• Consequence: PDSS2 NM_020381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 2 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDSS2	NM_020381.4	c.1009-332G>A		intron_variant	Intron 6 of 7	ENST00000369037.9	NP_065114.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDSS2	ENST00000369037.9	c.1009-332G>A		intron_variant	Intron 6 of 7	1	NM_020381.4	ENSP00000358033.4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35596 AN: 151966 Hom.: 5119 Cov.: 32

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.234 AC: 35621 AN: 152086 Hom.: 5130 Cov.: 32 AF XY: 0.239 AC XY: 17754 AN XY: 74350

African (AFR) AF: 0.0665 AC: 2761 AN: 41532

American (AMR) AF: 0.328 AC: 4999 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3468

East Asian (EAS) AF: 0.487 AC: 2524 AN: 5182

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4822

European-Finnish (FIN) AF: 0.282 AC: 2974 AN: 10564

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18639 AN: 67952

Other (OTH) AF: 0.263 AC: 557 AN: 2114

Alfa AF: 0.231 Hom.: 1566

Bravo AF: 0.232

Asia WGS AF: 0.390 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.5
DANN	Benign	0.82
PhyloP100		-0.064
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: rs3734679; hg19: chr6-107515390;