9-136508999-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP6_Very_StrongBS2
The NM_017617.5(NOTCH1):c.3042G>A(p.Thr1014=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000679 in 1,561,032 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1014T) has been classified as Likely benign.
Frequency
Consequence
NM_017617.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.3042G>A | p.Thr1014= | synonymous_variant | 19/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.2319G>A | p.Thr773= | synonymous_variant | 16/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.3042G>A | p.Thr1014= | synonymous_variant | 19/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152246Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000147 AC: 25AN: 170506Hom.: 1 AF XY: 0.000142 AC XY: 13AN XY: 91344
GnomAD4 exome AF: 0.0000454 AC: 64AN: 1408668Hom.: 1 Cov.: 35 AF XY: 0.0000489 AC XY: 34AN XY: 695964
GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152364Hom.: 0 Cov.: 34 AF XY: 0.000268 AC XY: 20AN XY: 74512
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
NOTCH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 31, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2020 | - - |
Aortic valve disease 1 Benign:1
Benign, 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