NM_000539.3(RHO):c.936+1G>T AND Retinitis pigmentosa 4

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Sep 1, 2020
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:: RCV001265165.2

Allele description [Variation Report for NM_000539.3(RHO):c.936+1G>T]

NM_000539.3(RHO):c.936+1G>T

Gene:

RHO:rhodopsin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q22.1

Genomic location:

Preferred name:

NM_000539.3(RHO):c.936+1G>T

HGVS:

NC_000003.12:g.129532773G>T
NG_009115.1:g.9135G>T
NM_000539.3:c.936+1G>TMANE SELECT
NC_000003.11:g.129251616G>T

Nucleotide change:

IVS4AS, G-T, +1

Links:

OMIM: 180380.0026; dbSNP: rs776014770

NCBI 1000 Genomes Browser:

rs776014770

Molecular consequence:

NM_000539.3:c.936+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Retinitis pigmentosa 4 (RP4)
Synonyms:: RP 4; RETINITIS PIGMENTOSA, RHODOPSIN-RELATED
Identifiers:: MONDO: MONDO:0013395; MedGen: C3151001; Orphanet: 791; OMIM: 613731

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LOC127460392 [Homo sapiens]
LOC127460392 [Homo sapiens]
Gene ID:127460392

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000034161	OMIM	no assertion criteria provided	Pathogenic (Oct 19, 2017)	germline	literature only	Rosenfeld, P. J., Cowley, G. S., Hahn, L. B., Sandberg, M. A., Berson, E. L., Dryja, T. P. A null mutation within the rhodopsin gene in a family with autosomal recessive retinitis pigmentosa. (Abstract) Invest. Ophthal. Vis. Sci. 33: 1397, 1992.,
SCV001443252	Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 1, 2020)	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

SCV000034161

OMIM

no assertion criteria provided

Pathogenic
(Oct 19, 2017)

germline

literature only

Rosenfeld, P. J., Cowley, G. S., Hahn, L. B., Sandberg, M. A., Berson, E. L., Dryja, T. P. A null mutation within the rhodopsin gene in a family with autosomal recessive retinitis pigmentosa. (Abstract) Invest. Ophthal. Vis. Sci. 33: 1397, 1992.,

SCV001443252

Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 1, 2020)

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV000034161.2

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

Description

In screening a group of 117 control persons without RP for the nonsense mutation E249X (180380.0023) in the RHO gene, Rosenfeld et al. (1992) found a 28-year-old female who was heterozygous for a different potential null mutation. After detection by SSCP analysis, direct sequencing of polymerase chain reaction (PCR)-amplified DNA from this person revealed a heterozygous G-to-T substitution at position 4335 within intron 4 of the rhodopsin gene. Since it is located at the canonical GT of the first 2 nucleotides of the splice donor sequence, the mutation is expected to interfere with normal processing of intron 4 and thus could alter the carboxy-terminal 36 amino acids of the rhodopsin molecule. The woman was found to have a reduction in rod sensitivity that was similar to the decrease observed in the carriers of the E249X 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 Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals, SCV001443252.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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