NM_001298.3(CNGA3):c.847C>T (p.Arg283Trp) AND not provided

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Mar 7, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001222182.47

Allele description [Variation Report for NM_001298.3(CNGA3):c.847C>T (p.Arg283Trp)]

NM_001298.3(CNGA3):c.847C>T (p.Arg283Trp)

Gene:

CNGA3:cyclic nucleotide gated channel subunit alpha 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q11.2

Genomic location:

Preferred name:

NM_001298.3(CNGA3):c.847C>T (p.Arg283Trp)

Other names:

NP_001289.1:p.(Arg283Trp)

HGVS:

NC_000002.12:g.98396017C>T
NG_009097.1:g.54863C>T
NM_001079878.2:c.793C>T
NM_001298.3:c.847C>TMANE SELECT
NP_001073347.1:p.Arg265Trp
NP_001289.1:p.Arg283Trp
NP_001289.1:p.Arg283Trp
NC_000002.11:g.99012480C>T
NM_001298.2:c.847C>T
Q16281:p.Arg283Trp

Protein change:

R265W; ARG283TRP

Links:

UniProtKB: Q16281#VAR_010905; OMIM: 600053.0002; dbSNP: rs104893613

Molecular consequence:

NM_001079878.2:c.793C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001298.3:c.847C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001394271	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 7, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 9662398, 11536077, 24504161, 25637600, 26992781, 17693388, 20238023, 28492532
SCV001773382	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 26, 2021)	germline	clinical testing	Citation Link,
SCV001905566	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001956988	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001966736	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002063881	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Oct 1, 2022)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	4	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel.

Kohl S, Marx T, Giddings I, Jägle H, Jacobson SG, Apfelstedt-Sylla E, Zrenner E, Sharpe LT, Wissinger B.

Nat Genet. 1998 Jul;19(3):257-9.

PubMed [citation]

PMID:: 9662398

CNGA3 mutations in hereditary cone photoreceptor disorders.

Wissinger B, Gamer D, Jägle H, Giorda R, Marx T, Mayer S, Tippmann S, Broghammer M, Jurklies B, Rosenberg T, Jacobson SG, Sener EC, Tatlipinar S, Hoyng CB, Castellan C, Bitoun P, Andreasson S, Rudolph G, Kellner U, Lorenz B, Wolff G, Verellen-Dumoulin C, et al.

Am J Hum Genet. 2001 Oct;69(4):722-37. Epub 2001 Aug 30.

PubMed [citation]

PMID:: 11536077
PMCID:: PMC1226059

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001394271.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 283 of the CNGA3 protein (p.Arg283Trp). This variant is present in population databases (rs104893613, gnomAD 0.02%). This missense change has been observed in individual(s) with achromatopsia (PMID: 9662398, 11536077, 24504161, 25637600, 26992781). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 9474). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CNGA3 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CNGA3 function (PMID: 17693388, 20238023). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV001773382.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate a damaging effect consistent with loss-of-function (Muraki-Oda et al., 2007; Ding et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26992781, 31237654, 32141364, 20238023, 24504161, 9662398, 16319819, 17693388, 11536077, 30682209, 31877759, 32869108, 33562422, 32037395)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001905566.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001956988.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001966736.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV002063881.30

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		4	not provided	not provided	not provided

Last Updated: Mar 7, 2026

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