6-107210483-G-C

Position:

• chr6-107210483-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000369037.9(PDSS2):​c.964C>G​(p.Gln322Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,456,706 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PDSS2 ENST00000369037.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.31

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDSS2	NM_020381.4	c.964C>G	p.Gln322Glu	missense_variant	6/8	ENST00000369037.9	NP_065114.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDSS2	ENST00000369037.9	c.964C>G	p.Gln322Glu	missense_variant	6/8	1	NM_020381.4	ENSP00000358033	P1
PDSS2	ENST00000449027.1	c.139C>G	p.Gln47Glu	missense_variant	2/3	3		ENSP00000392613

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251146 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135782

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456706 Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2 AN XY: 725116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.21	T;.
Polyphen		0.73	P;.
Vest4		0.62
MutPred		0.73		Gain of helix (P = 0.132);.;
MVP		0.67
MPC		0.18
ClinPred		0.45	T
GERP RS		6.0
Varity_R		0.27
gMVP		0.39

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: rs118203955; hg19: chr6-107531687;