9-136500788-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_017617.5(NOTCH1):c.5698A>G(p.Ser1900Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1449224Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 721426
GnomAD4 genome AF: 0.00000656 AC: 1AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74510
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Uncertain:1
This sequence change replaces serine with glycine at codon 1900 of the NOTCH1 protein (p.Ser1900Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine and glycine. This variant is present in population databases (rs200190466, ExAC 0.01%) but has not been reported in the literature in individuals with a NOTCH1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at