rs1289556
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_052867.4(NALCN):āc.4416A>Cā(p.Ile1472=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,610,586 control chromosomes in the GnomAD database, including 114,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.44 ( 17334 hom., cov: 33)
Exomes š: 0.36 ( 97017 hom. )
Consequence
NALCN
NM_052867.4 synonymous
NM_052867.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.08
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=-0.48).
BP6
?
Variant 13-101067948-T-G is Benign according to our data. Variant chr13-101067948-T-G is described in ClinVar as [Benign]. Clinvar id is 262263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-101067948-T-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.08 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NALCN | NM_052867.4 | c.4416A>C | p.Ile1472= | synonymous_variant | 39/44 | ENST00000251127.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NALCN | ENST00000251127.11 | c.4416A>C | p.Ile1472= | synonymous_variant | 39/44 | 1 | NM_052867.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.443 AC: 67239AN: 151916Hom.: 17302 Cov.: 33
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GnomAD3 exomes AF: 0.341 AC: 85333AN: 250328Hom.: 16871 AF XY: 0.340 AC XY: 46007AN XY: 135212
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GnomAD4 exome AF: 0.356 AC: 518861AN: 1458552Hom.: 97017 Cov.: 32 AF XY: 0.355 AC XY: 257469AN XY: 725648
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GnomAD4 genome ? AF: 0.443 AC: 67305AN: 152034Hom.: 17334 Cov.: 33 AF XY: 0.433 AC XY: 32215AN XY: 74318
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 03, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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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