NM_001354768.3(NRL):c.416C>G (p.Ser139Trp) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 12, 2022
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:: RCV001939033.4

Allele description [Variation Report for NM_001354768.3(NRL):c.416C>G (p.Ser139Trp)]

NM_001354768.3(NRL):c.416C>G (p.Ser139Trp)

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.416C>G (p.Ser139Trp)

HGVS:

NC_000014.9:g.24081534G>C
NG_011697.2:g.38481C>G
NM_001354768.3:c.416C>GMANE SELECT
NM_001354769.1:c.416C>G
NM_001354770.2:c.101C>G
NM_006177.5:c.416C>G
NP_001341697.1:p.Ser139Trp
NP_001341698.1:p.Ser139Trp
NP_001341699.1:p.Ser34Trp
NP_006168.1:p.Ser139Trp
NC_000014.8:g.24550743G>C

Protein change:

S139W

Links:

dbSNP: rs2138870548

NCBI 1000 Genomes Browser:

rs2138870548

Molecular consequence:

NM_001354768.3:c.416C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354769.1:c.416C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354770.2:c.101C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006177.5:c.416C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

COP9 signalosome complex subunit 3 [Danio rerio]
COP9 signalosome complex subunit 3 [Danio rerio]
gi|53292634|ref|NP_955979.1|

Protein
PMC Links for Taxonomy (Select 1814) (64)
PMC
txid47871[Organism] (28288)
Protein
PetD, partial (chloroplast) [Aristolochia melanocephala]
PetD, partial (chloroplast) [Aristolochia melanocephala]
gi|1625643058|gb|QCF61421.1|

Protein
Danio rerio COP9 signalosome subunit 3 (cops3), mRNA
Danio rerio COP9 signalosome subunit 3 (cops3), mRNA
gi|53292633|ref|NM_199685.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002202767	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 12, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29186038, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002202767

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 12, 2022)

germline

clinical testing

PubMed (2)
[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

Molecular Screening of 43 Brazilian Families Diagnosed with Leber Congenital Amaurosis or Early-Onset Severe Retinal Dystrophy.

Porto FBO, Jones EM, Branch J, Soens ZT, Maia IM, Sena IFG, Sampaio SAM, Simões RT, Chen R.

Genes (Basel). 2017 Nov 29;8(12). doi:pii: E355. 10.3390/genes8120355.

PubMed [citation]

PMID:: 29186038
PMCID:: PMC5748673

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002202767.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (gnomAD no frequency). 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. 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. This missense change has been observed in individual(s) with NRL-related conditions (PMID: 29186038). This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 139 of the NRL protein (p.Ser139Trp).

#	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

ClinVar

Relating variation to medicine