NM_019098.5(CNGB3):c.446_447insT (p.Lys149fs) AND Achromatopsia 3

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 22, 2022
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:: RCV000411864.5

Allele description [Variation Report for NM_019098.5(CNGB3):c.446_447insT (p.Lys149fs)]

NM_019098.5(CNGB3):c.446_447insT (p.Lys149fs)

Gene:

CNGB3:cyclic nucleotide gated channel subunit beta 3 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_019098.5(CNGB3):c.446_447insT (p.Lys149fs)

HGVS:

NC_000008.11:g.86670990_86670991insA
NG_016980.1:g.77685_77686insT
NM_019098.5:c.446_447insTMANE SELECT
NP_061971.3:p.Lys149fs
NP_061971.3:p.Lys149fs
NC_000008.10:g.87683218_87683219insA
NM_019098.4:c.446_447insT

Protein change:

K149fs

Links:

OMIM: 605080.0005; dbSNP: rs748993388

NCBI 1000 Genomes Browser:

rs748993388

Molecular consequence:

NM_019098.5:c.446_447insT - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000485330	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Nov 20, 2015)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV002521267	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000485330

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Nov 20, 2015)

unknown

clinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV002521267

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 22, 2022)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate.

Rojas CV, María LS, Santos JL, Cortés F, Alliende MA.

Eur J Hum Genet. 2002 Oct;10(10):638-42.

PubMed [citation]

PMID:: 12357335

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Counsyl, SCV000485330.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV002521267.1

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

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000370100). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Oct 8, 2024

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