chr13-101055386-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_052867.4(NALCN):c.5126C>T(p.Ala1709Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000743 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. A1709T) has been classified as Uncertain significance.
Frequency
Consequence
NM_052867.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NALCN | NM_052867.4 | c.5126C>T | p.Ala1709Val | missense_variant | 44/44 | ENST00000251127.11 | |
NALCN-AS1 | NR_047687.1 | n.710G>A | non_coding_transcript_exon_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NALCN | ENST00000251127.11 | c.5126C>T | p.Ala1709Val | missense_variant | 44/44 | 1 | NM_052867.4 | P1 | |
NALCN-AS1 | ENST00000457843.1 | n.710G>A | non_coding_transcript_exon_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251422Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135880
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727224
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 14, 2020 | The c.5126C>T (p.A1709V) 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 5126, causing the alanine (A) at amino acid position 1709 to be replaced by a valine (V). Based on data from the Genome Aggregation Database (gnomAD) database, the NALCN c.5126C>T alteration was observed in 0.0007% (2/282822) of total alleles studied, with a frequency of 0.008% (2/24964) in the African subpopulation. This amino acid position is poorly conserved in available vertebrate species. The p.A1709V alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at