NM_000283.4:c.958G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_000283.4(PDE6B):c.958G>A(p.Val320Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,579,676 control chromosomes in the GnomAD database, including 789,598 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 76020 hom., cov: 32)

Exomes 𝑓: 1.0 ( 713578 hom. )

Consequence

PDE6B
NM_000283.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.61

Variant links:

Genes affected

PDE6B (HGNC:8786): (phosphodiesterase 6B) Photon absorption triggers a signaling cascade in rod photoreceptors that activates cGMP phosphodiesterase (PDE), resulting in the rapid hydrolysis of cGMP, closure of cGMP-gated cation channels, and hyperpolarization of the cell. PDE is a peripheral membrane heterotrimeric enzyme made up of alpha, beta, and gamma subunits. This gene encodes the beta subunit. Mutations in this gene result in retinitis pigmentosa and autosomal dominant congenital stationary night blindness. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

PDE6B links:

PDE6B-AS1 (HGNC:40438): (PDE6B antisense RNA 1)

PDE6B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a domain GAF 2 (size 177) in uniprot entity PDE6B_HUMAN there are 19 pathogenic changes around while only 1 benign (95%) in NM_000283.4

BP4

Computational evidence support a benign effect (MetaRNN=8.386741E-7).

BP6

Variant 4-654854-G-A is Benign according to our data. Variant chr4-654854-G-A is described in ClinVar as [Benign]. Clinvar id is 167436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-654854-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE6B	NM_000283.4 link	c.958G>A	p.Val320Ile	missense_variant	Exon 6 of 22	ENST00000496514.6	NP_000274.3	P35913-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE6B	ENST00000496514.6 link	c.958G>A	p.Val320Ile	missense_variant	Exon 6 of 22	1	NM_000283.4	ENSP00000420295.1		P35913-1

Frequencies

GnomAD3 genomes

AF:

0.999

AC:

152029

AN:

152138

Hom.:

75960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD3 exomes

AF:

1.00

AC:

251298

AN:

251346

Hom.:

125625

AF XY:

1.00

AC XY:

135871

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.997

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1427287

AN:

1427420

Hom.:

713578

Cov.:

AF XY:

1.00

AC XY:

712057

AN XY:

712116

show subpopulations

Gnomad4 AFR exome

AF:

0.997

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.999

AC:

152148

AN:

152256

Hom.:

76020

Cov.:

AF XY:

0.999

AC XY:

74384

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.997

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

1.00

Hom.:

104747

Bravo

AF:

0.999

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.997

AC:

4392

ESP6500EA

AF:

1.00

AC:

8600

ExAC

AF:

1.00

AC:

121377

Asia WGS

AF:

0.999

AC:

3476

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

- -

not specified

Benign:1

Sep 30, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital stationary night blindness autosomal dominant 2

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 40

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa

Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.18

.;T;.;.;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.53

T;T;T;T;T

MetaRNN

Benign

8.4e-7

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.2

N;N;.;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.65

N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.039

MPC

0.10

ClinPred

0.0036

GERP RS

4.7

Varity_R

0.024

gMVP

0.089

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