NM_145200.5(CABP4):c.370C>T (p.Arg124Cys) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Jan 6, 2025
Review status:: criteria provided, conflicting classifications

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:: RCV001049798.10

Allele description [Variation Report for NM_145200.5(CABP4):c.370C>T (p.Arg124Cys)]

NM_145200.5(CABP4):c.370C>T (p.Arg124Cys)

Gene:

CABP4:calcium binding protein 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_145200.5(CABP4):c.370C>T (p.Arg124Cys)

HGVS:

NC_000011.10:g.67456191C>T
NG_021211.1:g.5845C>T
NM_001300895.3:c.55C>T
NM_001300896.3:c.55C>T
NM_001379183.1:c.55C>T
NM_145200.5:c.370C>TMANE SELECT
NP_001287824.1:p.Arg19Cys
NP_001287825.1:p.Arg19Cys
NP_001366112.1:p.Arg19Cys
NP_660201.1:p.Arg124Cys
NC_000011.9:g.67223662C>T
NM_145200.3:c.370C>T
P57796:p.Arg124Cys

Protein change:

R124C; ARG124CYS

Links:

UniProtKB: P57796#VAR_029375; OMIM: 608965.0002; dbSNP: rs121917828

NCBI 1000 Genomes Browser:

rs121917828

Molecular consequence:

NM_001300895.3:c.55C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001300896.3:c.55C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379183.1:c.55C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_145200.5:c.370C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001213869	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 6, 2025)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16960802, 37734845, 28492532
SCV002072824	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 30, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001213869

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 6, 2025)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002072824

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 30, 2022)

germline

clinical testing

Citation Link

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

Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause autosomal recessive night blindness.

Zeitz C, Kloeckener-Gruissem B, Forster U, Kohl S, Magyar I, Wissinger B, Mátyás G, Borruat FX, Schorderet DF, Zrenner E, Munier FL, Berger W.

Am J Hum Genet. 2006 Oct;79(4):657-67. Epub 2006 Aug 23.

PubMed [citation]

PMID:: 16960802
PMCID:: PMC1592568

Diagnostic genome sequencing improves diagnostic yield: a prospective single-centre study in 1000 patients with inherited eye diseases.

Weisschuh N, Mazzola P, Zuleger T, Schaeferhoff K, Kühlewein L, Kortüm F, Witt D, Liebmann A, Falb R, Pohl L, Reith M, Stühn LG, Bertrand M, Müller A, Casadei N, Kelemen O, Kelbsch C, Kernstock C, Richter P, Sadler F, Demidov G, Schütz L, et al.

J Med Genet. 2024 Jan 19;61(2):186-195. doi: 10.1136/jmg-2023-109470.

PubMed [citation]

PMID:: 37734845
PMCID:: PMC10850689

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001213869.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 124 of the CABP4 protein (p.Arg124Cys). This variant is present in population databases (rs121917828, gnomAD 0.05%). This missense change has been observed in individual(s) with congenital stationary night blindness (PMID: 16960802, 37734845). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1953). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CABP4 protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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

From GeneDx, SCV002072824.2

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23099293, 31589614, 33369259, 34426522, 16960802, 35791102)

#	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

Last Updated: May 16, 2025

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