rs1043997
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7
The NM_000435.3(NOTCH3):c.2742A>T(p.Pro914=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P914P) has been classified as Benign.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NOTCH3
NM_000435.3 synonymous
NM_000435.3 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -9.66
Genes affected
NOTCH3 (HGNC:7883): (notch receptor 3) This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP7
?
Synonymous conserved (PhyloP=-9.66 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH3 | NM_000435.3 | c.2742A>T | p.Pro914= | synonymous_variant | 17/33 | ENST00000263388.7 | |
NOTCH3 | XM_005259924.5 | c.2586A>T | p.Pro862= | synonymous_variant | 16/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH3 | ENST00000263388.7 | c.2742A>T | p.Pro914= | synonymous_variant | 17/33 | 1 | NM_000435.3 | P1 | |
NOTCH3 | ENST00000601011.1 | c.2583A>T | p.Pro861= | synonymous_variant | 16/23 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1398888Hom.: 0 Cov.: 68 AF XY: 0.00 AC XY: 0AN XY: 690046
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1398888
Hom.:
Cov.:
68
AF XY:
AC XY:
0
AN XY:
690046
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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