2-98389666-C-T

Position:

chr2-98389666-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001298.3(CNGA3):c.458C>T(p.Thr153Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,696 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 3 hom., cov: 32)

Exomes 𝑓: 0.011 ( 98 hom. )

Consequence

CNGA3
NM_001298.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.694

Variant links:

Genes affected

CNGA3 (HGNC:2150): (cyclic nucleotide gated channel subunit alpha 3) This gene encodes a member of the cyclic nucleotide-gated cation channel protein family which is required for normal vision and olfactory signal transduction. Mutations in this gene are associated with achromatopsia (rod monochromacy) and color blindness. Two alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CNGA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070102513).

BP6

Variant 2-98389666-C-T is Benign according to our data. Variant chr2-98389666-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 285271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-98389666-C-T is described in Lovd as [Likely_benign]. Variant chr2-98389666-C-T is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA3	NM_001298.3 linkuse as main transcript	c.458C>T	p.Thr153Met	missense_variant	6/8	ENST00000272602.7	NP_001289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA3	ENST00000272602.7 linkuse as main transcript	c.458C>T	p.Thr153Met	missense_variant	6/8	1	NM_001298.3	ENSP00000272602	A1	Q16281-1
CNGA3	ENST00000436404.6 linkuse as main transcript	c.404C>T	p.Thr135Met	missense_variant	5/7	1		ENSP00000410070	P4	Q16281-2
CNGA3	ENST00000393503.2 linkuse as main transcript	n.463C>T		non_coding_transcript_exon_variant	2/2	4
CNGA3	ENST00000409937.1 linkuse as main transcript	n.611C>T		non_coding_transcript_exon_variant	6/8	2

Frequencies

GnomAD3 genomes

AF:

0.00825

AC:

1255

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00848

AC:

2133

AN:

251484

Hom.:

AF XY:

0.00870

AC XY:

1182

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00783

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00444

Gnomad FIN exome

AF:

0.00822

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.0109

AC:

15967

AN:

1461422

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

7774

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00847

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00441

Gnomad4 FIN exome

AF:

0.00900

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00824

AC:

1255

AN:

152274

Hom.:

Cov.:

AF XY:

0.00809

AC XY:

602

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00229

Gnomad4 AMR

AF:

0.00935

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00659

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00773

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.00856

AC:

1039

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0103

EpiControl

AF:

0.0104

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2021	See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	CNGA3: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 27, 2016

- -

Achromatopsia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.10

T;.;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.97

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.34

T;T;.;T

MetaRNN

Benign

0.0070

T;T;T;T

MetaSVM

Uncertain

-0.028

MutationAssessor

Benign

0.34

N;.;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.27

Sift

Benign

0.039

D;T;D;T

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.19

B;.;B;.

Vest4

0.24

MVP

0.90

MPC

0.12

ClinPred

0.015

GERP RS

-0.19

Varity_R

0.027

gMVP

0.26

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