NM_000435.3:c.2956T>G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_000435.3(NOTCH3):c.2956T>G(p.Cys986Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C986R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000435.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOTCH3 | ENST00000263388.7 | c.2956T>G | p.Cys986Gly | missense_variant | Exon 18 of 33 | 1 | NM_000435.3 | ENSP00000263388.1 | ||
NOTCH3 | ENST00000601011.1 | c.2797T>G | p.Cys933Gly | missense_variant | Exon 17 of 23 | 5 | ENSP00000473138.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.92e-7 AC: 1AN: 1445222Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 717690
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at