9-136517826-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PP2PP3_StrongPP5_Moderate
The NM_017617.5(NOTCH1):c.1367G>A(p.Cys456Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. C456C) has been classified as Likely benign.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.1367G>A | p.Cys456Tyr | missense_variant | 8/34 | ENST00000651671.1 | |
LOC124902310 | XR_007061865.1 | n.508-5492C>T | intron_variant, non_coding_transcript_variant | ||||
NOTCH1 | XM_011518717.3 | c.644G>A | p.Cys215Tyr | missense_variant | 5/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.1367G>A | p.Cys456Tyr | missense_variant | 8/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome Cov.: 35
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Molecular and Medical Genetics Group, King's College London | Feb 24, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at