10-93646057-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006204.4(PDE6C):c.1935+10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,479,756 control chromosomes in the GnomAD database, including 158,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14718 hom., cov: 32)

Exomes 𝑓: 0.46 ( 144151 hom. )

Consequence

PDE6C
NM_006204.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-93646057-C-A is Benign according to our data. Variant chr10-93646057-C-A is described in ClinVar as Benign. ClinVar VariationId is 259943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE6C	NM_006204.4 link	c.1935+10C>A		intron_variant	Intron 15 of 21	ENST00000371447.4	NP_006195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE6C	ENST00000371447.4 link	c.1935+10C>A		intron_variant	Intron 15 of 21	1	NM_006204.4	ENSP00000360502.3

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65920

AN:

151872

Hom.:

14714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.414

GnomAD2 exomes

AF:

0.457

AC:

114263

AN:

250124

AF XY:

0.462

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.404

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.482

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.464

AC:

615798

AN:

1327766

Hom.:

144151

Cov.:

AF XY:

0.467

AC XY:

311767

AN XY:

667986

show subpopulations

African (AFR)

AF:

0.309

AC:

9601

AN:

31072

American (AMR)

AF:

0.404

AC:

17981

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

11180

AN:

25284

East Asian (EAS)

AF:

0.430

AC:

16790

AN:

39066

South Asian (SAS)

AF:

0.473

AC:

39571

AN:

83606

European-Finnish (FIN)

AF:

0.538

AC:

28639

AN:

53184

Middle Eastern (MID)

AF:

0.434

AC:

2385

AN:

5496

European-Non Finnish (NFE)

AF:

0.469

AC:

464151

AN:

989458

Other (OTH)

AF:

0.454

AC:

25500

AN:

56130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

14011

28022

42033

56044

70055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12992

25984

38976

51968

64960

<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:

0.434

AC:

65939

AN:

151990

Hom.:

14718

Cov.:

AF XY:

0.437

AC XY:

32434

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.321

AC:

13304

AN:

41446

American (AMR)

AF:

0.425

AC:

6487

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1541

AN:

3470

East Asian (EAS)

AF:

0.409

AC:

2113

AN:

5164

South Asian (SAS)

AF:

0.473

AC:

2277

AN:

4810

European-Finnish (FIN)

AF:

0.554

AC:

5853

AN:

10568

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.484

AC:

32906

AN:

67958

Other (OTH)

AF:

0.417

AC:

880

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1828

3655

5483

7310

9138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.462

Hom.:

14067

Bravo

AF:

0.416

Asia WGS

AF:

0.456

AC:

1587

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cone dystrophy 4

Benign:2

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. -

Sep 05, 2021

Genome-Nilou Lab

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

(source)

DANN

Benign

0.53

PhyloP100

-1.2

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