chr6-107154074-T-TA

Position:

• chr6-107154074-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020381.4(PDSS2):​c.*544_*545insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,770 control chromosomes in the GnomAD database, including 4,695 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4672 hom., cov: 26)
  • Exomes 𝑓: 0.18 (23 hom.)
• Consequence: PDSS2 NM_020381.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0620

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 -10 ACMG points.

• BP6: Variant 6-107154074-T-TA is Benign according to our data. Variant chr6-107154074-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 354761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDSS2	NM_020381.4	c.*544_*545insT		3_prime_UTR_variant	8/8	ENST00000369037.9	NP_065114.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDSS2	ENST00000369037.9	c.*544_*545insT		3_prime_UTR_variant	8/8	1	NM_020381.4	ENSP00000358033	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 33766 AN: 149516 Hom.: 4672 Cov.: 26

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.182 AC: 575 AN: 3162 Hom.: 23 Cov.: 0 AF XY: 0.177 AC XY: 299 AN XY: 1692

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.226 AC: 33763 AN: 149608 Hom.: 4672 Cov.: 26 AF XY: 0.229 AC XY: 16714 AN XY: 72958

Gnomad4 AFR AF: 0.0573

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.213

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Coenzyme Q10 deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs35619837; hg19: chr6-107475278;