chr9-136513419-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP6_ModerateBS2
The NM_017617.5(NOTCH1):c.2326G>A(p.Val776Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V776L) has been classified as Uncertain significance.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.2326G>A | p.Val776Met | missense_variant | 14/34 | ENST00000651671.1 | |
LOC124902310 | XR_007061865.1 | n.507+3440C>T | intron_variant, non_coding_transcript_variant | ||||
NOTCH1 | XM_011518717.3 | c.1603G>A | p.Val535Met | missense_variant | 11/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.2326G>A | p.Val776Met | missense_variant | 14/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152240Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247780Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135008
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460566Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726572
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74384
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at