VCV000425431.41 - ClinVar

NM_178857.6(RP1L1):c.5959C>T (p.Gln1987Ter)

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.

(5)

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(3); Benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_178857.6(RP1L1):c.5959C>T (p.Gln1987Ter)

Variation ID: 425431 Accession: VCV000425431.41

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 8p23.1 8: 10608139 (GRCh38) [ NCBI UCSC ] 8: 10465649 (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 15, 2018	Oct 20, 2024	May 28, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_178857.6:c.5959C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_849188.4:p.Gln1987Ter	nonsense
NC_000008.11:g.10608139G>A
NC_000008.10:g.10465649G>A
NG_028035.1:g.51969C>T

Protein change

Q1987*

Other names

Canonical SPDI

NC_000008.11:10608138: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.

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

The Genome Aggregation Database (gnomAD) 0.00124

Exome Aggregation Consortium (ExAC) 0.00156

The Genome Aggregation Database (gnomAD), exomes 0.00163

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00195

Links

ClinGen: CA4623490 dbSNP: rs200846354 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.
RP1L1		-	-	GRCh38 GRCh38 GRCh37	1339	1468

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.
not provided	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	May 1, 2018	RCV000487849.28
Occult macular dystrophy	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	May 28, 2019	RCV000988031.10
Autosomal recessive retinitis pigmentosa	Pathogenic (1)	no assertion criteria provided	Sep 10, 2015	RCV001257841.2

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.
Uncertain significance (May 26, 2017)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000707628.2 First in ClinVar: Apr 02, 2018 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RP1L1 Number of individuals with the variant: 2 Sex: mixed
Uncertain significance (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Occult macular dystrophy Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001137580.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Jan 31, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Occult macular dystrophy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001320220.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Publications: PubMed (2) PubMed: 26355662‚ 22277662 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
Uncertain significance (May 01, 2018)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV000575541.32 First in ClinVar: May 08, 2017 Last updated: Oct 20, 2024	Number of individuals with the variant: 3
Pathogenic (Sep 10, 2015)	no assertion criteria provided Method: literature only	Autosomal recessive Retinitis Pigmentosa Affected status: yes Allele origin: germline	Faculty of Health Sciences, Beirut Arab University Accession: SCV001434704.1 First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020	Publications: PubMed (1) PubMed: 26355662 Number of individuals with the variant: 1 Ethnicity/Population group: Arab

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

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
Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies.	Patel N	Genetics in medicine : official journal of the American College of Medical Genetics	2016	PMID: 26355662
Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases.	Audo I	Orphanet journal of rare diseases	2012	PMID: 22277662
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RP1L1	-	-	-	-

Text-mined citations for rs200846354 ...

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 Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_178857.6(RP1L1):c.5959C>T (p.Gln1987Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs200846354 ...