NM_174878.3(CLRN1):c.118T>G (p.Cys40Gly) AND Usher syndrome type 3

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Feb 1, 2019
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:: RCV000004649.9

Allele description [Variation Report for NM_174878.3(CLRN1):c.118T>G (p.Cys40Gly)]

NM_174878.3(CLRN1):c.118T>G (p.Cys40Gly)

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.118T>G (p.Cys40Gly)

HGVS:

NC_000003.12:g.150972591A>C
NG_009168.1:g.5409T>G
NM_001195794.1:c.118T>G
NM_001256819.2:c.118T>G
NM_174878.3:c.118T>GMANE SELECT
NP_001182723.1:p.Cys40Gly
NP_001243748.1:p.Cys40Gly
NP_777367.1:p.Cys40Gly
LRG_700t1:c.118T>G
LRG_700:g.5409T>G
LRG_700p1:p.Cys40Gly
NC_000003.11:g.150690378A>C
NM_174878.2:c.118T>G
NR_046380.3:n.137T>G
P58418:p.Cys40Gly

Protein change:

C40G; CYS40GLY

Links:

UniProtKB: P58418#VAR_054555; OMIM: 606397.0008; dbSNP: rs121908143

NCBI 1000 Genomes Browser:

rs121908143

Molecular consequence:

NM_001195794.1:c.118T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001256819.2:c.118T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_174878.3:c.118T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_046380.3:n.137T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Usher syndrome type 3
Synonyms:: Usher Syndrome, Type III
Identifiers:: MONDO: MONDO:0016485; MedGen: C1568248

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000024823	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 2004)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001156372	Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2019)	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

SCV000024823

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 2004)

germline

literature only

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

SCV001156372

Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2019)

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	germline	yes	1	not provided	not provided	not provided	no	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability.

Aller E, Jaijo T, Oltra S, Alió J, Galán F, Nájera C, Beneyto M, Millán JM.

Clin Genet. 2004 Dec;66(6):525-9.

PubMed [citation]

PMID:: 15521980

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 OMIM, SCV000024823.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with Usher syndrome type IIIA (USH3A; 276902), Aller et al. (2004) identified homozygosity for a 118T-G transversion in the CLRN1 gene, resulting in a cys40-to-gly (C40G) mutation. Both parents and an unaffected sister were heterozygous for the mutation.

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

From Counsyl, SCV000800518.1

#	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 Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals, SCV001156372.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	no	clinical testing	PubMed (1)

#	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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000800518	Counsyl	flagged submission Reason: Older claim that does not account for recent evidence Notes: None (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Apr 19, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000800518

Counsyl

flagged submission

Reason: Older claim that does not account for recent evidence

Notes: None

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Apr 19, 2017)

unknown

clinical testing

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

Citation Link

Last Updated: Sep 29, 2024

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