VCV000317232.10 - ClinVar

NM_000326.5(RLBP1):c.875C>T (p.Thr292Met)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(3)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000326.5(RLBP1):c.875C>T (p.Thr292Met)

Variation ID: 317232 Accession: VCV000317232.10

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 15q26.1 15: 89210364 (GRCh38) [ NCBI UCSC ] 15: 89753595 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 6, 2016	Mar 10, 2024	Oct 1, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000326.5:c.875C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000317.1:p.Thr292Met	missense
NC_000015.10:g.89210364G>A
NC_000015.9:g.89753595G>A
NG_008116.1:g.16328C>T

Protein change

T292M

Other names

Canonical SPDI

NC_000015.10:89210363:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00004

The Genome Aggregation Database (gnomAD) 0.00006

Exome Aggregation Consortium (ExAC) 0.00007

Trans-Omics for Precision Medicine (TOPMed) 0.00007

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA7722155 dbSNP: rs201588178 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
RLBP1		-	-	GRCh38 GRCh37	387	428

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Retinitis Pigmentosa, Recessive	Likely benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000369084.5
not provided	Uncertain significance (1)	criteria provided, single submitter	Oct 24, 2022	RCV001203836.5
Retinal dystrophy	Uncertain significance (1)	criteria provided, single submitter	Oct 1, 2023	RCV003888735.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Retinitis Pigmentosa, Recessive Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000394091.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016	Publications: PubMed (1) PubMed: 22164218
Uncertain significance (Oct 24, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001375015.4 First in ClinVar: Jul 16, 2020 Last updated: Feb 07, 2023	Publications: PubMed (1) PubMed: 22164218 Comment: This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 292 of the RLBP1 protein (p.Thr292Met). … (more) This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 292 of the RLBP1 protein (p.Thr292Met). This variant is present in population databases (rs201588178, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 22164218). ClinVar contains an entry for this variant (Variation ID: 317232). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RLBP1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Oct 01, 2023)	criteria provided, single submitter (Submitter's publication) Method: research	Retinal dystrophy Affected status: yes Allele origin: germline	Dept Of Ophthalmology, Nagoya University Accession: SCV004704921.1 First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024

Comment:

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 292 of the RLBP1 protein (p.Thr292Met). This variant is present in population databases (rs201588178, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 22164218). ClinVar contains an entry for this variant (Variation ID: 317232). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RLBP1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mutation screening of multiple genes in Spanish patients with autosomal recessive retinitis pigmentosa by targeted resequencing.	González-del Pozo M	PloS one	2011	PMID: 22164218

Text-mined citations for rs201588178 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000326.5(RLBP1):c.875C>T (p.Thr292Met)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs201588178 ...