chr1-160343469-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_015331.3(NCSTN):c.73G>A(p.Val25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,457,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V25V) has been classified as Likely benign.
Frequency
Consequence
NM_015331.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCSTN | NM_015331.3 | c.73G>A | p.Val25Ile | missense_variant | 1/17 | ENST00000294785.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCSTN | ENST00000294785.10 | c.73G>A | p.Val25Ile | missense_variant | 1/17 | 1 | NM_015331.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000416 AC: 1AN: 240606Hom.: 0 AF XY: 0.00000771 AC XY: 1AN XY: 129682
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1457720Hom.: 0 Cov.: 31 AF XY: 0.00000690 AC XY: 5AN XY: 724704
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2022 | This variant is present in population databases (no rsID available, gnomAD 0.0009%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NCSTN protein function. ClinVar contains an entry for this variant (Variation ID: 1425278). This variant has not been reported in the literature in individuals affected with NCSTN-related conditions. This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 25 of the NCSTN protein (p.Val25Ile). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at