NM_052867.4(NALCN):c.1245C>A (p.Tyr415Ter) AND NALCN-related disorder

Germline classification:: Pathogenic (1 submission)
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:: RCV003335867.1

Allele description [Variation Report for NM_052867.4(NALCN):c.1245C>A (p.Tyr415Ter)]

NM_052867.4(NALCN):c.1245C>A (p.Tyr415Ter)

Genes:

LOC126861831:P300/CBP strongly-dependent group 1 enhancer GRCh37_chr13:101909917-101911116 [Gene]
NALCN:sodium leak channel, non-selective [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q33.1

Genomic location:

Preferred name:

NM_052867.4(NALCN):c.1245C>A (p.Tyr415Ter)

HGVS:

NC_000013.11:g.101258464G>T
NG_053176.1:g.163743C>A
NG_086329.1:g.999G>T
NM_001350748.2:c.1245C>A
NM_001350749.2:c.1245C>A
NM_001350750.2:c.1158C>A
NM_001350751.2:c.1158C>A
NM_052867.4:c.1245C>AMANE SELECT
NP_001337677.1:p.Tyr415Ter
NP_001337678.1:p.Tyr415Ter
NP_001337679.1:p.Tyr386Ter
NP_001337680.1:p.Tyr386Ter
NP_443099.1:p.Tyr415Ter
NC_000013.10:g.101910815G>T
NM_052867.2:c.1245C>A

Protein change:

Y386*

Links:

dbSNP: rs1426944195

NCBI 1000 Genomes Browser:

rs1426944195

Molecular consequence:

NM_001350748.2:c.1245C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001350749.2:c.1245C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001350750.2:c.1158C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001350751.2:c.1158C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_052867.4:c.1245C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: NALCN-related disorder
Synonyms:: NALCN-related disorders; NALCN-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004046054	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	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

SCV004046054

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046054.1

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

Description

This nonsense variant found in exon 11 of 44 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has not been previously reported or functionally characterized in the literature to our knowledge. Loss-of-function variation in NALCN is an established mechanism of disease (PMID: 23749988). The c.1245C>A (p.Tyr415Ter) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.0004% (1/251220) and is absent in the homozygous state, thus is presumed to be rare. Based on the available evidence, the c.1245C>A (p.Tyr415Ter) variant is classified as Pathogenic.

#	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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