NM_052867.4:c.4977C>G
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS1
The NM_052867.4(NALCN):c.4977C>G(p.Asp1659Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,613,936 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1659A) has been classified as Uncertain significance.
Frequency
Consequence
NM_052867.4 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Benign. The variant received -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NALCN | NM_052867.4 | c.4977C>G | p.Asp1659Glu | missense_variant | Exon 43 of 44 | ENST00000251127.11 | NP_443099.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00148 AC: 225AN: 152172Hom.: 1 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000426 AC: 107AN: 250996 AF XY: 0.000324 show subpopulations
GnomAD4 exome AF: 0.000177 AC: 259AN: 1461646Hom.: 0 Cov.: 30 AF XY: 0.000153 AC XY: 111AN XY: 727166 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00148 AC: 225AN: 152290Hom.: 1 Cov.: 32 AF XY: 0.00142 AC XY: 106AN XY: 74468 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
NALCN-related disorder Benign:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at