NM_001012720.2(RGR):c.532T>C (p.Phe178Leu) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 11, 2023
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:: RCV000484976.5

Allele description [Variation Report for NM_001012720.2(RGR):c.532T>C (p.Phe178Leu)]

NM_001012720.2(RGR):c.532T>C (p.Phe178Leu)

Gene:

RGR:retinal G protein coupled receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.1

Genomic location:

Preferred name:

NM_001012720.2(RGR):c.532T>C (p.Phe178Leu)

HGVS:

NC_000010.11:g.84254345T>C
NG_009106.1:g.14293T>C
NM_001012720.2:c.532T>CMANE SELECT
NM_001012722.2:c.532T>C
NM_002921.4:c.544T>C
NP_001012738.1:p.Phe178Leu
NP_001012740.1:p.Phe178Leu
NP_002912.2:p.Phe182Leu
NC_000010.10:g.86014101T>C
NM_001012720.1:c.532T>C

Protein change:

F178L

Links:

dbSNP: rs201379107

NCBI 1000 Genomes Browser:

rs201379107

Molecular consequence:

NM_001012720.2:c.532T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001012722.2:c.532T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002921.4:c.544T>C - 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
SCV000573094	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Feb 23, 2017)	germline	clinical testing	Citation Link,
SCV001374285	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000573094

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Feb 23, 2017)

germline

clinical testing

Citation Link,

SCV001374285

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 11, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	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

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 GeneDx, SCV000573094.4

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

Description

The F178L variant in the RGR gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 1/66,740 (0.001%) alleles from individuals of European background in the ExAC dataset and in 6/60,310 (0.01%) alleles from presumably healthy individuals undergoing testing at GeneDx (Lek et al., 2016). The F178L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution is located within a helical transmembrane domain and occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret F178L as a variant of uncertain significance.

#	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		not provided	not provided	not provided	not provided

From Invitae, SCV001374285.4

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

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 178 of the RGR protein (p.Phe178Leu). This variant is present in population databases (rs201379107, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with RGR-related conditions. ClinVar contains an entry for this variant (Variation ID: 423397). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.

#	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: Jun 9, 2024

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