chr9-136504896-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_017617.5(NOTCH1):c.4795G>A(p.Val1599Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,584,424 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V1599V) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.4795G>A | p.Val1599Met | missense_variant | 26/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.4072G>A | p.Val1358Met | missense_variant | 23/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.4795G>A | p.Val1599Met | missense_variant | 26/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000201 AC: 4AN: 198576Hom.: 0 AF XY: 0.0000186 AC XY: 2AN XY: 107670
GnomAD4 exome AF: 0.0000161 AC: 23AN: 1432106Hom.: 1 Cov.: 33 AF XY: 0.0000141 AC XY: 10AN XY: 709692
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74478
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2023 | - - |
Aortic valve disease 1;C4014970:Adams-Oliver syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
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