rs714550

chr10-93629284-G-Achr10-93629284-G-Cchr10-93629284-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006204.4(PDE6C):c.1098G>A(p.Ala366=) 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:7

Conservation

PhyloP100: 0.0920

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-93629284-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
PDE6C	NM_006204.4 linkuse as main transcript	c.1098G>A	p.Ala366=	synonymous_variant	8/22	ENST00000371447.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE6C	ENST00000371447.4 linkuse as main transcript	c.1098G>A	p.Ala366=	synonymous_variant	8/22	1	NM_006204.4	P1

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

GnomAD3 exomes

AF:

0.353

AC:

88694

AN:

251332

Hom.:

16202

AF XY:

0.347

AC XY:

47106

AN XY:

135838

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 SAS exome

AF:

0.305

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

Gnomad4 AFR exome

AF:

0.429

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.466

Gnomad4 SAS exome

AF:

0.306

Gnomad4 FIN exome

AF:

0.327

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.367

AC:

55831

AN:

151986

Hom.:

10476

Cov.:

AF XY:

0.366

AC XY:

27172

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.429

Gnomad4 AMR

AF:

0.385

Gnomad4 ASJ

AF:

0.315

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.302

Gnomad4 FIN

AF:

0.322

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.352

Alfa

AF:

0.337

Hom.:

11028

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Achromatopsia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

Cadd

Benign

6.6

Dann

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over