NM_019098.5(CNGB3):c.467C>T (p.Ser156Phe) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 7, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000815424.5

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_019098.5:c.467C>TMANE SELECT
NP_061971.3:p.Ser156Phe
NP_061971.3:p.Ser156Phe
NC_000008.10:g.87683198G>A
NM_019098.4:c.467C>T

Protein change:

S156F

Links:

dbSNP: rs139207764

NCBI 1000 Genomes Browser:

rs139207764

Molecular consequence:

NM_019098.5:c.467C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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olfactory receptor 5B3-like [Mus caroli]
olfactory receptor 5B3-like [Mus caroli]
gi|1195665560|ref|XP_021010307.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000955875	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 7, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15657609, 25616768, 28795510, 26106334, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000955875

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 7, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.

Kohl S, Varsanyi B, Antunes GA, Baumann B, Hoyng CB, Jägle H, Rosenberg T, Kellner U, Lorenz B, Salati R, Jurklies B, Farkas A, Andreasson S, Weleber RG, Jacobson SG, Rudolph G, Castellan C, Dollfus H, Legius E, Anastasi M, Bitoun P, Lev D, et al.

Eur J Hum Genet. 2005 Mar;13(3):302-8.

PubMed [citation]

PMID:: 15657609

Genetics and Disease Expression in the CNGA3 Form of Achromatopsia: Steps on the Path to Gene Therapy.

Zelinger L, Cideciyan AV, Kohl S, Schwartz SB, Rosenmann A, Eli D, Sumaroka A, Roman AJ, Luo X, Brown C, Rosin B, Blumenfeld A, Wissinger B, Jacobson SG, Banin E, Sharon D.

Ophthalmology. 2015 May;122(5):997-1007. doi: 10.1016/j.ophtha.2014.11.025. Epub 2015 Jan 21.

PubMed [citation]

PMID:: 25616768

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000955875.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 156 of the CNGB3 protein (p.Ser156Phe). This variant is present in population databases (rs139207764, gnomAD 0.04%). This missense change has been observed in individual(s) with achromatopsia (PMID: 15657609, 25616768, 28795510). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 427671). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CNGB3 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CNGB3 function (PMID: 26106334). 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

Last Updated: Nov 10, 2024

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