NM_001354768.3(NRL):c.152C>T (p.Pro51Leu) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 12, 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:: RCV001172074.27

Allele description [Variation Report for NM_001354768.3(NRL):c.152C>T (p.Pro51Leu)]

NM_001354768.3(NRL):c.152C>T (p.Pro51Leu)

Gene:

NRL:neural retina leucine zipper [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_001354768.3(NRL):c.152C>T (p.Pro51Leu)

HGVS:

NC_000014.9:g.24082697G>A
NG_011697.2:g.37318C>T
NM_001354768.3:c.152C>TMANE SELECT
NM_001354769.1:c.152C>T
NM_001354770.2:c.66+86C>T
NM_006177.5:c.152C>T
NP_001341697.1:p.Pro51Leu
NP_001341698.1:p.Pro51Leu
NP_006168.1:p.Pro51Leu
NC_000014.8:g.24551906G>A
NC_000014.8:g.24551906G>A

Protein change:

P51L

Links:

dbSNP: rs2036353653

NCBI 1000 Genomes Browser:

rs2036353653

Molecular consequence:

NM_001354770.2:c.66+86C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354768.3:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354769.1:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006177.5:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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peroxisomal membrane protein PEX14 isoform X4 [Homo sapiens]
peroxisomal membrane protein PEX14 isoform X4 [Homo sapiens]
gi|767904635|ref|XP_011539882.1|

Protein
Leucine-rich repeat protein kinase family protein [Arabidopsis thaliana]
Leucine-rich repeat protein kinase family protein [Arabidopsis thaliana]
Gene ID:827827

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001335011	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Mar 1, 2020)	germline	clinical testing	Citation Link,
SCV002196595	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 12, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15591106, 17335001, 11385710, 15994872, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001335011

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Mar 1, 2020)

germline

clinical testing

Citation Link,

SCV002196595

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 12, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function.

Nishiguchi KM, Friedman JS, Sandberg MA, Swaroop A, Berson EL, Dryja TP.

Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17819-24. Epub 2004 Dec 9.

PubMed [citation]

PMID:: 15591106
PMCID:: PMC535407

Retinopathy mutations in the bZIP protein NRL alter phosphorylation and transcriptional activity.

Kanda A, Friedman JS, Nishiguchi KM, Swaroop A.

Hum Mutat. 2007 Jun;28(6):589-98.

PubMed [citation]

PMID:: 17335001

See all PubMed Citations (5)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001335011.25

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002196595.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro51 amino acid residue in NRL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15591106; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects NRL function (PMID: 17335001). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 916413). This variant is also known as 2316C>T. This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 11385710, 15994872). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 51 of the NRL protein (p.Pro51Leu).

#	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

Last Updated: Oct 20, 2024

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