chr13-101055348-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_052867.4(NALCN):c.5164C>T(p.Arg1722Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1722Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_052867.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NALCN | NM_052867.4 | c.5164C>T | p.Arg1722Trp | missense_variant | 44/44 | ENST00000251127.11 | |
NALCN-AS1 | NR_047687.1 | n.672G>A | non_coding_transcript_exon_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NALCN | ENST00000251127.11 | c.5164C>T | p.Arg1722Trp | missense_variant | 44/44 | 1 | NM_052867.4 | P1 | |
NALCN-AS1 | ENST00000457843.1 | n.672G>A | non_coding_transcript_exon_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251328Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135822
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461800Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727204
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74436
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2022 | The c.5164C>T (p.R1722W) alteration is located in exon 44 (coding exon 43) of the NALCN gene. This alteration results from a C to T substitution at nucleotide position 5164, causing the arginine (R) at amino acid position 1722 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 30, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at