9-136515543-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PP2PP3_StrongBP6
The NM_017617.5(NOTCH1):c.1843G>A(p.Gly615Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,611,590 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G615G) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.1843G>A | p.Gly615Arg | missense_variant | 11/34 | ENST00000651671.1 | |
LOC124902310 | XR_007061865.1 | n.507+5564C>T | intron_variant, non_coding_transcript_variant | ||||
NOTCH1 | XM_011518717.3 | c.1120G>A | p.Gly374Arg | missense_variant | 8/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.1843G>A | p.Gly615Arg | missense_variant | 11/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000818 AC: 2AN: 244464Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133598
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1459384Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 14AN XY: 726068
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 31, 2021 | - - |
Adams-Oliver syndrome 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at