NM_000554.6(CRX):c.8C>T (p.Ala3Val) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 18, 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:: RCV001057955.5

Allele description

NM_000554.6(CRX):c.8C>T (p.Ala3Val)

Gene:

CRX:cone-rod homeobox [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.33

Genomic location:

Preferred name:

NM_000554.6(CRX):c.8C>T (p.Ala3Val)

HGVS:

NC_000019.10:g.47834451C>T
NG_008605.1:g.17610C>T
NM_000554.6:c.8C>TMANE SELECT
NP_000545.1:p.Ala3Val
NC_000019.9:g.48337708C>T
NM_000554.4:c.8C>T

Protein change:

A3V

Links:

dbSNP: rs762715327

NCBI 1000 Genomes Browser:

rs762715327

Molecular consequence:

NM_000554.6:c.8C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Leber congenital amaurosis 7 (LCA7)
Identifiers:: MONDO: MONDO:0013449; MedGen: C3151192; Orphanet: 65; OMIM: 613829

Name:: Cone-rod dystrophy 2 (CORD2)
Synonyms:: CONE-ROD RETINAL DYSTROPHY; Cone-rod retinal dystrophy 2
Identifiers:: MONDO: MONDO:0007362; MedGen: C3489532; Orphanet: 1872; OMIM: 120970

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001222485	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 18, 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

SCV001222485

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 18, 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	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 Invitae, SCV001222485.5

#	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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3 of the CRX protein (p.Ala3Val). This variant is present in population databases (rs762715327, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CRX-related conditions. ClinVar contains an entry for this variant (Variation ID: 853189). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CRX protein function with a negative predictive value of 80%. 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 23, 2024

ClinVar

Relating variation to medicine