Genetic Variant NM_020381.4:c.*311G>A (chr6-107154308-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020381.4(PDSS2):c.*311G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 361,272 control chromosomes in the GnomAD database, including 747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.056 ( 262 hom., cov: 33)

Exomes 𝑓: 0.061 ( 485 hom. )

Consequence

PDSS2
NM_020381.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.405

Publications

2 publications found

Variant links:

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

PDSS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 6-107154308-C-T is Benign according to our data. Variant chr6-107154308-C-T is described in ClinVar as [Benign]. Clinvar id is 1293935.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDSS2	NM_020381.4 link	c.*311G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000369037.9	NP_065114.3	Q86YH6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDSS2	ENST00000369037.9 link	c.*311G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_020381.4	ENSP00000358033.4		Q86YH6-1

Frequencies

GnomAD3 genomes

AF:

0.0556

AC:

8462

AN:

152102

Hom.:

262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0522

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0222

Gnomad FIN

AF:

0.0786

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0777

Gnomad OTH

AF:

0.0504

GnomAD4 exome

AF:

0.0615

AC:

12855

AN:

209052

Hom.:

485

Cov.:

AF XY:

0.0570

AC XY:

6512

AN XY:

114252

show subpopulations

African (AFR)

AF:

0.0305

AC:

178

AN:

5838

American (AMR)

AF:

0.0512

AC:

480

AN:

9372

Ashkenazi Jewish (ASJ)

AF:

0.0230

AC:

119

AN:

5184

East Asian (EAS)

AF:

0.000219

AC:

AN:

9146

South Asian (SAS)

AF:

0.0295

AC:

1132

AN:

38324

European-Finnish (FIN)

AF:

0.0816

AC:

757

AN:

9276

Middle Eastern (MID)

AF:

0.0597

AC:

AN:

754

European-Non Finnish (NFE)

AF:

0.0787

AC:

9495

AN:

120654

Other (OTH)

AF:

0.0616

AC:

647

AN:

10504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

588

1176

1765

2353

2941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0556

AC:

8461

AN:

152220

Hom.:

262

Cov.:

AF XY:

0.0551

AC XY:

4099

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0295

AC:

1227

AN:

41532

American (AMR)

AF:

0.0521

AC:

796

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0224

AC:

108

AN:

4824

European-Finnish (FIN)

AF:

0.0786

AC:

832

AN:

10590

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0777

AC:

5285

AN:

68024

Other (OTH)

AF:

0.0499

AC:

105

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

424

847

1271

1694

2118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0314

Hom.:

Bravo

AF:

0.0538

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_020381.4:c.*311G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over