NM_174878.3(CLRN1):c.189C>A (p.Tyr63Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 7, 2023
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:: RCV001384937.4

Allele description [Variation Report for NM_174878.3(CLRN1):c.189C>A (p.Tyr63Ter)]

NM_174878.3(CLRN1):c.189C>A (p.Tyr63Ter)

Gene:

CLRN1:clarin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q25.1

Genomic location:

Preferred name:

NM_174878.3(CLRN1):c.189C>A (p.Tyr63Ter)

HGVS:

NC_000003.12:g.150972520G>T
NG_009168.1:g.5480C>A
NM_001195794.1:c.189C>A
NM_001256819.2:c.189C>A
NM_174878.3:c.189C>AMANE SELECT
NP_001182723.1:p.Tyr63Ter
NP_001243748.1:p.Tyr63Ter
NP_777367.1:p.Tyr63Ter
LRG_700t1:c.189C>A
LRG_700:g.5480C>A
LRG_700p1:p.Tyr63Ter
NC_000003.11:g.150690307G>T
NM_174878.3:c.189C>A
NR_046380.3:n.208C>A
c.189C>A
p.Tyr63X

Protein change:

Y63*; TYR63TER

Links:

OMIM: 606397.0006; dbSNP: rs111033267

NCBI 1000 Genomes Browser:

rs111033267

Molecular consequence:

NR_046380.3:n.208C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001195794.1:c.189C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001256819.2:c.189C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_174878.3:c.189C>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001584632	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 7, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11524702, 24498627, 12080385, 23304067, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001584632

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 7, 2023)

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

Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3.

Joensuu T, Hämäläinen R, Yuan B, Johnson C, Tegelberg S, Gasparini P, Zelante L, Pirvola U, Pakarinen L, Lehesjoki AE, de la Chapelle A, Sankila EM.

Am J Hum Genet. 2001 Oct;69(4):673-84. Epub 2001 Aug 27. Erratum in: Am J Hum Genet 2001 Nov;69(5):1160.

PubMed [citation]

PMID:: 11524702
PMCID:: PMC1226054

Experience of targeted Usher exome sequencing as a clinical test.

Besnard T, García-García G, Baux D, Vaché C, Faugère V, Larrieu L, Léonard S, Millan JM, Malcolm S, Claustres M, Roux AF.

Mol Genet Genomic Med. 2014 Jan;2(1):30-43. doi: 10.1002/mgg3.25. Epub 2013 Jul 10.

PubMed [citation]

PMID:: 24498627
PMCID:: PMC3907913

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001584632.4

#	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 creates a premature translational stop signal (p.Tyr63*) in the CLRN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLRN1 are known to be pathogenic (PMID: 11524702, 24498627). This variant is present in population databases (rs111033267, gnomAD 0.008%). This premature translational stop signal has been observed in individuals with Usher syndrome (PMID: 12080385, 23304067). ClinVar contains an entry for this variant (Variation ID: 4397). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: Jun 17, 2024

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