NM_019098.5(CNGB3):c.467C>T (p.Ser156Phe) AND Achromatopsia 3

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Dec 14, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000498220.3

Allele description [Variation Report for NM_019098.5(CNGB3):c.467C>T (p.Ser156Phe)]

NM_019098.5(CNGB3):c.467C>T (p.Ser156Phe)

Gene:
CNGB3:cyclic nucleotide gated channel subunit beta 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q21.3
Genomic location:
Preferred name:
NM_019098.5(CNGB3):c.467C>T (p.Ser156Phe)
HGVS:
  • NC_000008.11:g.86670970G>A
  • NG_016980.1:g.77706C>T
  • NM_019098.4:c.467C>T
  • NM_019098.5:c.467C>TMANE SELECT
  • NP_061971.3:p.Ser156Phe
  • NP_061971.3:p.Ser156Phe
  • NC_000008.10:g.87683198G>A
Protein change:
S156F
Links:
dbSNP: rs139207764
NCBI 1000 Genomes Browser:
rs139207764
Molecular consequence:
  • NM_019098.4:c.467C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_019098.5:c.467C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Achromatopsia 3 (ACHM3)
Synonyms:
ROD MONOCHROMACY 1; ROD MONOCHROMATISM 1; Pingelapese blindness; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009875; MedGen: C1849792; Orphanet: 49382; OMIM: 262300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000575805Molecular Genetics Laboratory,Institute for Ophthalmic Researchno assertion criteria providedLikely pathogenic
(Mar 27, 2017)
germlineresearch

PubMed (1)
[See all records that cite this PMID]

SCV000795326Counsylcriteria provided, single submitter
Uncertain significance
(Nov 3, 2017)
unknownclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000916239Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Likely pathogenic
(Dec 14, 2018)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedresearch
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

CNGB3 mutation spectrum including copy number variations in 552 achromatopsia patients.

Mayer AK, Van Cauwenbergh C, Rother C, Baumann B, Reuter P, De Baere E, Wissinger B, Kohl S; ACHM Study Group..

Hum Mutat. 2017 Nov;38(11):1579-1591. doi: 10.1002/humu.23311. Epub 2017 Aug 28.

PubMed [citation]
PMID:
28795510

CNGB3-achromatopsia clinical trial with CNTF: diminished rod pathway responses with no evidence of improvement in cone function.

Zein WM, Jeffrey BG, Wiley HE, Turriff AE, Tumminia SJ, Tao W, Bush RA, Marangoni D, Wen R, Wei LL, Sieving PA.

Invest Ophthalmol Vis Sci. 2014 Sep 9;55(10):6301-8. doi: 10.1167/iovs.14-14860.

PubMed [citation]
PMID:
25205868
PMCID:
PMC4191169
See all PubMed Citations (5)

Details of each submission

From Molecular Genetics Laboratory,Institute for Ophthalmic Research, SCV000575805.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV000795326.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV000916239.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The CNGB3 c.467C>T (p.Ser156Phe) missense variant has been reported in three studies and identified in at least four unrelated compound heterozygotes, all affected with achromatopsia (Kohl et al. 2005; Zein et al. 2014; Zelinger et al. 2015). The variant was absent from 100 healthy controls but is reported at a frequency of 0.000394 in the Ashkenazi Jewish population in the Genome Aggregation Database. Meighan et al. (2015) performed functional studies using Xenopus oocytes and the p.Ser156Phe variant was found not to interfere with the formation of functional A3+B3 channels or to cause significant changes to CNG channel behavior compared to wild type. The variant is not found in a highly conserved region of the protein (Meighan et al. 2015). Based on the evidence, the p.Ser156Phe variant is classified as likely pathogenic for achromatopsia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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