chr9-136506911-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP2PP3BP6BS2
The NM_017617.5(NOTCH1):c.3706C>T(p.Pro1236Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,611,642 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1236L) has been classified as Uncertain significance.
Frequency
Consequence
NM_017617.5 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 |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.3706C>T | p.Pro1236Ser | missense_variant | 23/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.2983C>T | p.Pro995Ser | missense_variant | 20/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.3706C>T | p.Pro1236Ser | missense_variant | 23/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000206 AC: 5AN: 242980Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 132926
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1459410Hom.: 0 Cov.: 34 AF XY: 0.0000207 AC XY: 15AN XY: 725978
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 2022 | Has been reported as a variant of uncertain significance in a patient with BAV and TAAD (Proost et al., 2015); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25907466) - |
Adams-Oliver syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at