NM_000390.4(CHM):c.715C>T (p.Arg239Ter) AND Choroideremia

Germline classification:: Pathogenic (4 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:: RCV000763635.7

Allele description [Variation Report for NM_000390.4(CHM):c.715C>T (p.Arg239Ter)]

NM_000390.4(CHM):c.715C>T (p.Arg239Ter)

Gene:

CHM:CHM Rab escort protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq21.2

Genomic location:

Preferred name:

NM_000390.4(CHM):c.715C>T (p.Arg239Ter)

HGVS:

NC_000023.11:g.85958965G>A
NG_009874.2:g.93598C>T
NM_000390.4:c.715C>TMANE SELECT
NM_001320959.1:c.271C>T
NM_001362517.1:c.271C>T
NM_001362518.2:c.271C>T
NM_001362519.1:c.271C>T
NP_000381.1:p.Arg239Ter
NP_001307888.1:p.Arg91Ter
NP_001349446.1:p.Arg91Ter
NP_001349447.1:p.Arg91Ter
NP_001349448.1:p.Arg91Ter
LRG_699t1:c.715C>T
LRG_699:g.93598C>T
NC_000023.10:g.85213970G>A
NM_000390.2:c.715C>T

Protein change:

R239*

Links:

dbSNP: rs776256380

NCBI 1000 Genomes Browser:

rs776256380

Molecular consequence:

NM_000390.4:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001320959.1:c.271C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001362517.1:c.271C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001362518.2:c.271C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001362519.1:c.271C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Choroideremia (CHM)
Synonyms:: Progressive tapetochoroidal dystrophy
Identifiers:: MONDO: MONDO:0010557; MedGen: C0008525; Orphanet: 180; OMIM: 303100; Human Phenotype Ontology: HP:0001139

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000894505	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001160984	Sharon lab, Hadassah-Hebrew University Medical Center	no assertion criteria provided	Pathogenic (Jun 23, 2019)	inherited	research
SCV002089135	Natera, Inc.	no assertion criteria provided	Pathogenic (Oct 14, 2020)	germline	clinical testing
SCV002521110	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16087855, 25741868

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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	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Stop mutations in exon 6 of the choroideremia gene, CHM, associated with preservation of the electroretinogram.

Francis PJ, Fishman GA, Trzupek KM, MacDonald IM, Stone EM, Weleber RG.

Arch Ophthalmol. 2005 Aug;123(8):1146-9. No abstract available.

PubMed [citation]

PMID:: 16087855

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

PMC

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.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV000894505.1

#	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 Sharon lab, Hadassah-Hebrew University Medical Center, SCV001160984.1

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

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

From Natera, Inc., SCV002089135.1

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

From 3billion, SCV002521110.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Stop-gained (nonsense): 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 with clinical assertions and evidence for the classification (ClinVar ID: VCV000285756 / PMID: 16087855). 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: Jun 17, 2024

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