rs1555730176
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000435.3(NOTCH3):c.194G>T(p.Cys65Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C65S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000435.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH3 | NM_000435.3 | c.194G>T | p.Cys65Phe | missense_variant | 2/33 | ENST00000263388.7 | |
NOTCH3 | XM_005259924.5 | c.194G>T | p.Cys65Phe | missense_variant | 2/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH3 | ENST00000263388.7 | c.194G>T | p.Cys65Phe | missense_variant | 2/33 | 1 | NM_000435.3 | P1 | |
NOTCH3 | ENST00000601011.1 | c.191G>T | p.Cys64Phe | missense_variant | 2/23 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD4 exome Cov.: 35
GnomAD4 genome ? Cov.: 29
ClinVar
Submissions by phenotype
Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues | Mar 05, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at