10-93612977-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006204.4(PDE6C):c.252G>A(p.Leu84Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,613,762 control chromosomes in the GnomAD database, including 26,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L84L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.19 ( 2801 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23305 hom. )

Consequence

PDE6C
NM_006204.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.499

Publications

9 publications found

Variant links:

Genes affected

PDE6C (HGNC:8787): (phosphodiesterase 6C) This gene encodes the alpha-prime subunit of cone phosphodiesterase, which is composed of a homodimer of two alpha-prime subunits and 3 smaller proteins of 11, 13, and 15 kDa. Mutations in this gene are associated with cone dystrophy type 4 (COD4). [provided by RefSeq, Mar 2010]

PDE6C Gene-Disease associations (from GenCC):

cone dystrophy 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
achromatopsia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PDE6C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 10-93612977-G-A is Benign according to our data. Variant chr10-93612977-G-A is described in ClinVar as Benign. ClinVar VariationId is 95346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.499 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE6C	NM_006204.4 link	c.252G>A	p.Leu84Leu	synonymous_variant	Exon 1 of 22	ENST00000371447.4	NP_006195.3	P51160

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE6C	ENST00000371447.4 link	c.252G>A	p.Leu84Leu	synonymous_variant	Exon 1 of 22	1	NM_006204.4	ENSP00000360502.3		P51160

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28325

AN:

152020

Hom.:

2792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.180

GnomAD2 exomes

AF:

0.162

AC:

40604

AN:

250660

AF XY:

0.164

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.175

AC:

256456

AN:

1461624

Hom.:

23305

Cov.:

AF XY:

0.176

AC XY:

127681

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.239

AC:

7990

AN:

33478

American (AMR)

AF:

0.115

AC:

5147

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

6548

AN:

26128

East Asian (EAS)

AF:

0.0990

AC:

3932

AN:

39698

South Asian (SAS)

AF:

0.134

AC:

11540

AN:

86252

European-Finnish (FIN)

AF:

0.114

AC:

6081

AN:

53344

Middle Eastern (MID)

AF:

0.241

AC:

1384

AN:

5752

European-Non Finnish (NFE)

AF:

0.182

AC:

202790

AN:

1111880

Other (OTH)

AF:

0.183

AC:

11044

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

13268

26536

39805

53073

66341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7108

14216

21324

28432

35540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.186

AC:

28367

AN:

152138

Hom.:

2801

Cov.:

AF XY:

0.182

AC XY:

13540

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.233

AC:

9681

AN:

41480

American (AMR)

AF:

0.153

AC:

2346

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

912

AN:

3468

East Asian (EAS)

AF:

0.107

AC:

554

AN:

5158

South Asian (SAS)

AF:

0.124

AC:

597

AN:

4826

European-Finnish (FIN)

AF:

0.104

AC:

1109

AN:

10616

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.184

AC:

12490

AN:

67982

Other (OTH)

AF:

0.185

AC:

390

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1150

2300

3451

4601

5751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.130

Hom.:

314

Bravo

AF:

0.194

Asia WGS

AF:

0.140

AC:

486

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Sep 19, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 18, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Achromatopsia

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Cone dystrophy 4

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

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

-0.47

CADD

Benign

6.8

(source)

DANN

Benign

0.65

PhyloP100

0.50

PromoterAI

0.0092

Neutral

(source)

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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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