rs78817184
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_052867.4(NALCN):c.4977C>T(p.Asp1659Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,613,936 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 22 hom. )
Consequence
NALCN
NM_052867.4 synonymous
NM_052867.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0910
Genes affected
NALCN (HGNC:19082): (sodium leak channel, non-selective) This gene encodes a voltage-independent, nonselective cation channel which belongs to a family of voltage-gated sodium and calcium channels that regulates the resting membrane potential and excitability of neurons. This family is expressed throughout the nervous system and conducts a persistent sodium leak current that contributes to tonic neuronal excitability. The encoded protein forms a channelosome complex that includes G-protein-coupled receptors, UNC-79, UNC-80, NCA localization factor-1, and src family tyrosine kinases. Naturally occurring mutations in this gene are associated with infantile neuroaxonal dystrophy, infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) syndrome, and congenital contractures of the limbs and face with hypotonia and developmental delay (CLIFAHDD) syndrome. A knockout of the orthologous gene in mice results in paralysis with a severely disrupted respiratory rhythm, and lethality within 24 hours after birth. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 13-101057985-G-A is Benign according to our data. Variant chr13-101057985-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-101057985-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.091 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00302 (460/152290) while in subpopulation NFE AF= 0.00497 (338/68026). AF 95% confidence interval is 0.00453. There are 2 homozygotes in gnomad4. There are 193 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AD,AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NALCN | NM_052867.4 | c.4977C>T | p.Asp1659Asp | synonymous_variant | Exon 43 of 44 | ENST00000251127.11 | NP_443099.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00302 AC: 459AN: 152172Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00302 AC: 758AN: 250996Hom.: 2 AF XY: 0.00312 AC XY: 423AN XY: 135694
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GnomAD4 exome AF: 0.00333 AC: 4869AN: 1461646Hom.: 22 Cov.: 30 AF XY: 0.00343 AC XY: 2492AN XY: 727166
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GnomAD4 genome 0.00302 AC: 460AN: 152290Hom.: 2 Cov.: 32 AF XY: 0.00259 AC XY: 193AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Oct 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
NALCN: BP4, BP7, BS2 -
Jan 15, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Oct 08, 2020
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
NALCN-related disorder Benign:1
Jun 11, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at