rs714550

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006204.4(PDE6C):c.1098G>A(p.Ala366Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,603,472 control chromosomes in the GnomAD database, including 95,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10476 hom., cov: 32)

Exomes 𝑓: 0.34 ( 84681 hom. )

Consequence

PDE6C
NM_006204.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0920

Publications

18 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 10-93629284-G-A is Benign according to our data. Variant chr10-93629284-G-A is described in ClinVar as Benign. ClinVar VariationId is 259938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.092 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE6C	NM_006204.4 link	c.1098G>A	p.Ala366Ala	synonymous_variant	Exon 8 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.1098G>A	p.Ala366Ala	synonymous_variant	Exon 8 of 22	1	NM_006204.4	ENSP00000360502.3		P51160

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55760

AN:

151868

Hom.:

10454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.303

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.350

GnomAD2 exomes

AF:

0.353

AC:

88694

AN:

251332

AF XY:

0.347

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.459

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.337

AC:

489322

AN:

1451486

Hom.:

84681

Cov.:

AF XY:

0.336

AC XY:

243104

AN XY:

722700

show subpopulations

African (AFR)

AF:

0.429

AC:

14252

AN:

33250

American (AMR)

AF:

0.397

AC:

17765

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

8430

AN:

26080

East Asian (EAS)

AF:

0.466

AC:

18475

AN:

39626

South Asian (SAS)

AF:

0.306

AC:

26363

AN:

86018

European-Finnish (FIN)

AF:

0.327

AC:

17464

AN:

53388

Middle Eastern (MID)

AF:

0.333

AC:

1918

AN:

5752

European-Non Finnish (NFE)

AF:

0.330

AC:

363530

AN:

1102658

Other (OTH)

AF:

0.352

AC:

21125

AN:

60014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

16559

33118

49676

66235

82794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11822

23644

35466

47288

59110

<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:

0.367

AC:

55831

AN:

151986

Hom.:

10476

Cov.:

AF XY:

0.366

AC XY:

27172

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.429

AC:

17771

AN:

41450

American (AMR)

AF:

0.385

AC:

5876

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1092

AN:

3468

East Asian (EAS)

AF:

0.465

AC:

2399

AN:

5154

South Asian (SAS)

AF:

0.302

AC:

1454

AN:

4812

European-Finnish (FIN)

AF:

0.322

AC:

3400

AN:

10552

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.333

AC:

22614

AN:

67958

Other (OTH)

AF:

0.352

AC:

743

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1831

3663

5494

7326

9157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.341

Hom.:

14107

Bravo

AF:

0.377

Asia WGS

AF:

0.407

AC:

1415

AN:

3478

EpiCase

AF:

0.338

EpiControl

AF:

0.338

ClinVar

Significance: Benign

Submissions summary: Benign:8

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

Mar 03, 2015

GeneDx

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.41

CADD

Benign

6.6

(source)

DANN

Benign

0.70

PhyloP100

0.092

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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