9-136523014-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_017617.5(NOTCH1):āc.578G>Cā(p.Gly193Ala) variant causes a missense change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.0 ( 0 hom., cov: 34)
Exomes š: 0.0000072 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NOTCH1
NM_017617.5 missense
NM_017617.5 missense
Scores
5
12
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.81
Genes affected
NOTCH1 (HGNC:7881): (notch receptor 1) This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor plays a role in the development of numerous cell and tissue types. Mutations in this gene are associated with aortic valve disease, Adams-Oliver syndrome, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and head and neck squamous cell carcinoma. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.578G>C | p.Gly193Ala | missense_variant | Exon 4 of 34 | ENST00000651671.1 | NP_060087.3 | |
NOTCH1 | XM_011518717.3 | c.20-3449G>C | intron_variant | Intron 1 of 30 | XP_011517019.2 | |||
LOC124902310 | XR_007061865.1 | n.508-304C>G | intron_variant | Intron 1 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152166Hom.: 0 Cov.: 34 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000717 AC: 10AN: 1395372Hom.: 0 Cov.: 31 AF XY: 0.00000872 AC XY: 6AN XY: 688416
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GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 152166Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74326
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Data not reliable, filtered out with message: AC0;AS_VQSR
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at G193 (P = 0.0611);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at