9-136500796-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_017617.5(NOTCH1):c.5690C>T(p.Thr1897Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000275 in 1,600,614 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T1897T) has been classified as Likely benign.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.5690C>T | p.Thr1897Met | missense_variant | 31/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.4967C>T | p.Thr1656Met | missense_variant | 28/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.5690C>T | p.Thr1897Met | missense_variant | 31/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000296 AC: 7AN: 236456Hom.: 0 AF XY: 0.0000384 AC XY: 5AN XY: 130102
GnomAD4 exome AF: 0.0000297 AC: 43AN: 1448348Hom.: 0 Cov.: 32 AF XY: 0.0000305 AC XY: 22AN XY: 721002
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74388
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 23, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 26, 2015 | The p.T1897M variant (also known as c.5690C>T), located in coding exon 31 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 5690. The threonine at codon 1897 is replaced by methionine, an amino acid with some similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6245 samples (12490 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrates, however methionine is the reference amino acid in one species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
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