Variant 17-81651029-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_002602.4(PDE6G):c.*45G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,367,448 control chromosomes in the GnomAD database, including 119,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17492 hom., cov: 32)

Exomes 𝑓: 0.39 ( 101965 hom. )

Consequence

PDE6G
NM_002602.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.309

Variant links:

Genes affected

PDE6G (HGNC:8789): (phosphodiesterase 6G) This gene encodes the gamma subunit of cyclic GMP-phosphodiesterase, which is composed of alpha- and beta- catalytic subunits and two identical, inhibitory gamma subunits. This gene is expressed in rod photoreceptors and functions in the phototransduction signaling cascade. It is also expressed in a variety of other tissues, and has been shown to regulate the c-Src protein kinase and G-protein-coupled receptor kinase 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

PDE6G links:

PDE6G (HGNC:):

PDE6G 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=-0.87).

BP6

Variant 17-81651029-C-T is Benign according to our data. Variant chr17-81651029-C-T is described in ClinVar as [Benign]. Clinvar id is 325860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6G	NM_002602.4 linkuse as main transcript	c.*45G>A		3_prime_UTR_variant	4/4	ENST00000331056.10	NP_002593.1	P18545

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6G	ENST00000331056.10 linkuse as main transcript	c.*45G>A		3_prime_UTR_variant	4/4	1	NM_002602.4	ENSP00000328412.5		P18545

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69578

AN:

151830

Hom.:

17452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.597

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.598

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.471

AC:

117503

AN:

249602

Hom.:

31258

AF XY:

0.461

AC XY:

62297

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.678

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.785

Gnomad SAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.391

AC:

474761

AN:

1215500

Hom.:

101965

Cov.:

AF XY:

0.395

AC XY:

243503

AN XY:

616946

show subpopulations

Gnomad4 AFR exome

AF:

0.607

Gnomad4 AMR exome

AF:

0.665

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.751

Gnomad4 SAS exome

AF:

0.567

Gnomad4 FIN exome

AF:

0.332

Gnomad4 NFE exome

AF:

0.340

Gnomad4 OTH exome

AF:

0.417

GnomAD4 genome

AF:

0.459

AC:

69672

AN:

151948

Hom.:

17492

Cov.:

AF XY:

0.462

AC XY:

34344

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.597

Gnomad4 AMR

AF:

0.546

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.781

Gnomad4 SAS

AF:

0.598

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.367

Hom.:

17609

Bravo

AF:

0.483

Asia WGS

AF:

0.706

AC:

2457

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Retinitis pigmentosa 57

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Retinitis pigmentosa

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

DANN

Benign

0.41

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

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