rs1057516040
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Moderate
The NM_052867.4(NALCN):c.985A>G(p.Arg329Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R329T) has been classified as Likely pathogenic.
Frequency
Consequence
NM_052867.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NALCN | NM_052867.4 | c.985A>G | p.Arg329Gly | missense_variant | 9/44 | ENST00000251127.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NALCN | ENST00000251127.11 | c.985A>G | p.Arg329Gly | missense_variant | 9/44 | 1 | NM_052867.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Congenital contractures of the limbs and face, hypotonia, and developmental delay Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Jul 21, 2015 | This substitution is predicted to result in a change of an arginine to a glycine at position 329, NP_443099.1, p.(Arg329Gly). The amino acid at this position is highly conserved, and in the transmembrane domain. This substitution is predicted to be disease-causing by in silico models, and is novel. Grantham assessment is likely deleterious based on conservation and amino acid properties. This variant was confirmed to be de novo, and was identified in a child with clinical features of CLIFAHDD syndrome. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at