NM_019098.5(CNGB3):c.1579-1G>A AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 3, 2019
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:: RCV001092878.22

Allele description [Variation Report for NM_019098.5(CNGB3):c.1579-1G>A]

NM_019098.5(CNGB3):c.1579-1G>A

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.1579-1G>A

HGVS:

NC_000008.11:g.86611672C>T
NG_016980.1:g.137004G>A
NM_019098.5:c.1579-1G>AMANE SELECT
NC_000008.10:g.87623900C>T
NM_019098.4:c.1579-1G>A

Links:

dbSNP: rs1057516504

NCBI 1000 Genomes Browser:

rs1057516504

Molecular consequence:

NM_019098.5:c.1579-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV001249601	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Dec 1, 2018)	germline	clinical testing	Citation Link,
SCV001375525	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 3, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 25558176, 28795510, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001249601

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Dec 1, 2018)

germline

clinical testing

Citation Link,

SCV001375525

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 3, 2019)

germline

clinical testing

PubMed (4)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Five novel CNGB3 gene mutations in Polish patients with achromatopsia.

Wawrocka A, Kohl S, Baumann B, Walczak-Sztulpa J, Wicher K, Skorczyk-Werner A, Krawczynski MR.

Mol Vis. 2014;20:1732-9.

PubMed [citation]

PMID:: 25558176
PMCID:: PMC4279706

See all PubMed Citations (4)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001249601.21

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

From Invitae, SCV001375525.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CNGB3 are known to be pathogenic (PMID: 28795510). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with achromatopsia (PMID: 25558176, 28795510). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 370459). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 13 of the CNGB3 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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: May 12, 2024

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