rs1555729077
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000435.3(NOTCH3):c.1232C>T(p.Thr411Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,292 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T411S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000435.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH3 | NM_000435.3 | c.1232C>T | p.Thr411Met | missense_variant | 8/33 | ENST00000263388.7 | |
NOTCH3 | XM_005259924.5 | c.1232C>T | p.Thr411Met | missense_variant | 8/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH3 | ENST00000263388.7 | c.1232C>T | p.Thr411Met | missense_variant | 8/33 | 1 | NM_000435.3 | P1 | |
NOTCH3 | ENST00000601011.1 | c.1229C>T | p.Thr410Met | missense_variant | 8/23 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152278Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461014Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726836
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74400
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 12, 2017 | Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at