Variant chr10-93635488-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006204.4(PDE6C):c.1270-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,606,120 control chromosomes in the GnomAD database, including 3,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 272 hom., cov: 32)

Exomes 𝑓: 0.069 ( 3680 hom. )

Consequence

PDE6C
NM_006204.4 intron

Scores

Splicing: ADA: 0.00001187

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.111

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-93635488-C-T is Benign according to our data. Variant chr10-93635488-C-T is described in ClinVar as [Benign]. Clinvar id is 259941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-93635488-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6C	NM_006204.4 linkuse as main transcript	c.1270-9C>T		intron_variant		ENST00000371447.4	NP_006195.3	P51160

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6C	ENST00000371447.4 linkuse as main transcript	c.1270-9C>T		intron_variant		1	NM_006204.4	ENSP00000360502.3		P51160

Frequencies

GnomAD3 genomes

AF:

0.0543

AC:

8264

AN:

152066

Hom.:

274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.0596

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.0595

Gnomad SAS

AF:

0.0635

Gnomad FIN

AF:

0.0570

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0747

Gnomad OTH

AF:

0.0526

GnomAD3 exomes

AF:

0.0615

AC:

15435

AN:

251128

Hom.:

530

AF XY:

0.0632

AC XY:

8574

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.0467

Gnomad ASJ exome

AF:

0.0478

Gnomad EAS exome

AF:

0.0671

Gnomad SAS exome

AF:

0.0721

Gnomad FIN exome

AF:

0.0627

Gnomad NFE exome

AF:

0.0697

Gnomad OTH exome

AF:

0.0684

GnomAD4 exome

AF:

0.0687

AC:

99831

AN:

1453936

Hom.:

3680

Cov.:

AF XY:

0.0695

AC XY:

50275

AN XY:

723858

show subpopulations

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.0489

Gnomad4 ASJ exome

AF:

0.0486

Gnomad4 EAS exome

AF:

0.0647

Gnomad4 SAS exome

AF:

0.0704

Gnomad4 FIN exome

AF:

0.0625

Gnomad4 NFE exome

AF:

0.0720

Gnomad4 OTH exome

AF:

0.0682

GnomAD4 genome

AF:

0.0543

AC:

8263

AN:

152184

Hom.:

272

Cov.:

AF XY:

0.0542

AC XY:

4030

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.0595

Gnomad4 ASJ

AF:

0.0484

Gnomad4 EAS

AF:

0.0595

Gnomad4 SAS

AF:

0.0632

Gnomad4 FIN

AF:

0.0570

Gnomad4 NFE

AF:

0.0747

Gnomad4 OTH

AF:

0.0544

Alfa

AF:

0.0629

Hom.:

185

Bravo

AF:

0.0515

Asia WGS

AF:

0.0670

AC:

235

AN:

3476

EpiCase

AF:

0.0695

EpiControl

AF:

0.0678

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.84

CADD

Benign

1.5

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0020

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

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