rs1037236860
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_017617.5(NOTCH1):c.1205C>T(p.Ser402Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000748 in 1,603,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S402S) has been classified as Likely benign.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.1205C>T | p.Ser402Leu | missense_variant | 7/34 | ENST00000651671.1 | |
LOC124902310 | XR_007061865.1 | n.508-5131G>A | intron_variant, non_coding_transcript_variant | ||||
NOTCH1 | XM_011518717.3 | c.482C>T | p.Ser161Leu | missense_variant | 4/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.1205C>T | p.Ser402Leu | missense_variant | 7/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000131 AC: 3AN: 228582Hom.: 0 AF XY: 0.00000802 AC XY: 1AN XY: 124712
GnomAD4 exome AF: 0.00000689 AC: 10AN: 1451024Hom.: 0 Cov.: 34 AF XY: 0.00000693 AC XY: 5AN XY: 721004
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 28, 2021 | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Aortic valve disease 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at