NM_001354768.3(NRL):c.227C>T (p.Ala76Val) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 3, 2023
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:: RCV001319005.5

Allele description [Variation Report for NM_001354768.3(NRL):c.227C>T (p.Ala76Val)]

NM_001354768.3(NRL):c.227C>T (p.Ala76Val)

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.227C>T (p.Ala76Val)

HGVS:

NC_000014.9:g.24082622G>A
NG_011697.2:g.37393C>T
NM_001354768.3:c.227C>TMANE SELECT
NM_001354769.1:c.227C>T
NM_001354770.2:c.66+161C>T
NM_006177.5:c.227C>T
NP_001341697.1:p.Ala76Val
NP_001341698.1:p.Ala76Val
NP_006168.1:p.Ala76Val
NC_000014.8:g.24551831G>A
NM_006177.3:c.227C>T

Protein change:

A76V

Links:

dbSNP: rs149921817

NCBI 1000 Genomes Browser:

rs149921817

Molecular consequence:

NM_001354770.2:c.66+161C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354768.3:c.227C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354769.1:c.227C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006177.5:c.227C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001509729	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15591106, 23534816, 17335001, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001509729

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 3, 2023)

germline

clinical testing

PubMed (4)
[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	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

Detection of novel genetic variation in autosomal dominant retinitis pigmentosa.

Borràs E, de Sousa Dias M, Hernan I, Pascual B, Mañé B, Gamundi MJ, Delás B, Carballo M.

Clin Genet. 2013 Nov;84(5):441-52. doi: 10.1111/cge.12151. Epub 2013 Apr 15.

PubMed [citation]

PMID:: 23534816

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001509729.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 76 of the NRL protein (p.Ala76Val). This variant is present in population databases (rs149921817, gnomAD 0.02%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 15591106, 23534816). ClinVar contains an entry for this variant (Variation ID: 882489). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on NRL function (PMID: 17335001). 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.

#	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: Sep 29, 2024

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