rs140567100
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000435.3(NOTCH3):c.5895G>T(p.Lys1965Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,260 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
NOTCH3
NM_000435.3 missense
NM_000435.3 missense
Scores
1
7
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0680
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NOTCH3 | ENST00000263388.7 | c.5895G>T | p.Lys1965Asn | missense_variant | Exon 32 of 33 | 1 | NM_000435.3 | ENSP00000263388.1 | ||
| NOTCH3 | ENST00000597756.1 | c.408G>T | p.Lys136Asn | missense_variant | Exon 3 of 3 | 2 | ENSP00000468879.1 | |||
| NOTCH3 | ENST00000595514.1 | n.*103G>T | non_coding_transcript_exon_variant | Exon 4 of 5 | 3 | ENSP00000470661.1 | ||||
| NOTCH3 | ENST00000595514.1 | n.*103G>T | 3_prime_UTR_variant | Exon 4 of 5 | 3 | ENSP00000470661.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32
GnomAD3 genomes
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32
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GnomAD4 exome Cov.: 34
GnomAD4 exome
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34
GnomAD4 genome 0.00000657 AC: 1AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74434
GnomAD4 genome
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of ubiquitination at K1965 (P = 0.0087);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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
Publications
No publications associated with this variant yet.