1-160343408-AG-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_015331.3(NCSTN):c.17del(p.Gly6ValfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G5G) has been classified as Benign.
Frequency
Consequence
NM_015331.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCSTN | NM_015331.3 | c.17del | p.Gly6ValfsTer22 | frameshift_variant | 1/17 | ENST00000294785.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCSTN | ENST00000294785.10 | c.17del | p.Gly6ValfsTer22 | frameshift_variant | 1/17 | 1 | NM_015331.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460806Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726602
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 02, 2018 | The c.17delG variant in the NCSTN gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.17delG variant causes a frameshift starting with codon Glycine 6, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 22 of the new reading frame, denoted p.Gly6ValfsX22. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.17delG variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.17delG as a pathogenic variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at