rs377594681
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 7P and 2B. PM2PP2PP3_StrongBP6_Moderate
The NM_017617.5(NOTCH1):c.3788G>T(p.Arg1263Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,870 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1263H) has been classified as Uncertain significance.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.3788G>T | p.Arg1263Leu | missense_variant | 23/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.3065G>T | p.Arg1022Leu | missense_variant | 20/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.3788G>T | p.Arg1263Leu | missense_variant | 23/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.00000817 AC: 2AN: 244722Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133660
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459870Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 726196
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at