9-136509007-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.3034G>A(p.Gly1012Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,561,828 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. G1012G) 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.3034G>A | p.Gly1012Ser | missense_variant | 19/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.2311G>A | p.Gly771Ser | missense_variant | 16/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.3034G>A | p.Gly1012Ser | missense_variant | 19/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000233 AC: 4AN: 171378Hom.: 0 AF XY: 0.0000327 AC XY: 3AN XY: 91856
GnomAD4 exome AF: 0.0000213 AC: 30AN: 1409608Hom.: 0 Cov.: 35 AF XY: 0.0000215 AC XY: 15AN XY: 696506
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 2023 | The c.3034G>A (p.G1012S) alteration is located in exon 19 (coding exon 19) of the NOTCH1 gene. This alteration results from a G to A substitution at nucleotide position 3034, causing the glycine (G) at amino acid position 1012 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Adams-Oliver syndrome 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 15, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at