Variant 8-86644671-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019098.5(CNGB3):c.1006G>A(p.Glu336Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 1,583,540 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CNGB3
NM_019098.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.48

Variant links:

Genes affected

CNGB3 (HGNC:2153): (cyclic nucleotide gated channel subunit beta 3) This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. [provided by RefSeq, Feb 2010]

CNGB3 links:

CNGB3 (HGNC:):

CNGB3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB3	NM_019098.5 linkuse as main transcript	c.1006G>A	p.Glu336Lys	missense_variant	9/18	ENST00000320005.6	NP_061971.3	Q9NQW8-1
CNGB3	XM_011517138.3 linkuse as main transcript	c.592G>A	p.Glu198Lys	missense_variant	7/16		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNGB3	ENST00000320005.6 linkuse as main transcript	c.1006G>A	p.Glu336Lys	missense_variant	9/18	1	NM_019098.5	ENSP00000316605.5	Q9NQW8-1
CNGB3	ENST00000681546.1 linkuse as main transcript	n.826G>A		non_coding_transcript_exon_variant	4/13
CNGB3	ENST00000681746.1 linkuse as main transcript	n.1006G>A		non_coding_transcript_exon_variant	9/19			ENSP00000505959.1	A0A5J6DSN8

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1433034

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

712876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000365

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000664

AC:

AN:

150506

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.69

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.36

Sift

Uncertain

0.015

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.58

MutPred

0.63

Gain of methylation at E336 (P = 0.007);

MVP

0.84

MPC

0.21

ClinPred

1.0

GERP RS

6.0

Varity_R

0.67

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.36

Position offset: 15

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over