dbSNP rs12781149: PDE6C:p.Asp94Asp (chr10-93613007-C-T) – ACMG Classification: Benign (-19 pts)

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.282C>T(p.Asp94Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,614,046 control chromosomes in the GnomAD database, including 7,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 502 hom., cov: 32)

Exomes 𝑓: 0.093 ( 6956 hom. )

Consequence

PDE6C
NM_006204.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.620

Publications

8 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
PDE6C-related retinopathy
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=-0.36).

BP6

Variant 10-93613007-C-T is Benign according to our data. Variant chr10-93613007-C-T is described in ClinVar as Benign. ClinVar VariationId is 95347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006204.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6C	NM_006204.4	MANE Select	c.282C>T	p.Asp94Asp	synonymous	Exon 1 of 22	NP_006195.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6C	ENST00000371447.4	TSL:1 MANE Select	c.282C>T	p.Asp94Asp	synonymous	Exon 1 of 22	ENSP00000360502.3	P51160

Frequencies

GnomAD3 genomes

AF:

0.0709

AC:

10790

AN:

152162

Hom.:

503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.0719

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0731

Gnomad FIN

AF:

0.0726

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.0722

GnomAD2 exomes

AF:

0.0789

AC:

19783

AN:

250676

AF XY:

0.0827

show subpopulations

Gnomad AFR exome

AF:

0.0176

Gnomad AMR exome

AF:

0.0585

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0771

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.0914

GnomAD4 exome

AF:

0.0935

AC:

136661

AN:

1461766

Hom.:

6956

Cov.:

AF XY:

0.0946

AC XY:

68797

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.0162

AC:

543

AN:

33478

American (AMR)

AF:

0.0622

AC:

2780

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

3669

AN:

26136

East Asian (EAS)

AF:

0.000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0835

AC:

7204

AN:

86258

European-Finnish (FIN)

AF:

0.0768

AC:

4103

AN:

53390

Middle Eastern (MID)

AF:

0.117

AC:

672

AN:

5768

European-Non Finnish (NFE)

AF:

0.101

AC:

112140

AN:

1111930

Other (OTH)

AF:

0.0916

AC:

5530

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

7801

15601

23402

31202

39003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3998

7996

11994

15992

19990

<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:

0.0708

AC:

10784

AN:

152280

Hom.:

502

Cov.:

AF XY:

0.0702

AC XY:

5227

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0179

AC:

743

AN:

41560

American (AMR)

AF:

0.0717

AC:

1097

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

472

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5172

South Asian (SAS)

AF:

0.0737

AC:

356

AN:

4828

European-Finnish (FIN)

AF:

0.0726

AC:

771

AN:

10618

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

7001

AN:

68016

Other (OTH)

AF:

0.0714

AC:

151

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

509

1018

1527

2036

2545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0940

Hom.:

884

Bravo

AF:

0.0684

Asia WGS

AF:

0.0330

AC:

117

AN:

3478

EpiCase

AF:

0.107

EpiControl

AF:

0.110

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Achromatopsia (1)

Cone dystrophy 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.8

(source)

DANN

Benign

0.74

PhyloP100

0.62

PromoterAI

0.0096

Neutral

(source)

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over