11-94799659-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_130847.3(AMOTL1):c.469C>T(p.Arg157Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_130847.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AMOTL1 | NM_130847.3 | c.469C>T | p.Arg157Cys | missense_variant | Exon 3 of 13 | ENST00000433060.3 | NP_570899.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AMOTL1 | ENST00000433060.3 | c.469C>T | p.Arg157Cys | missense_variant | Exon 3 of 13 | 1 | NM_130847.3 | ENSP00000387739.2 | ||
AMOTL1 | ENST00000317829.12 | c.319C>T | p.Arg107Cys | missense_variant | Exon 2 of 12 | 1 | ENSP00000320968.8 | |||
AMOTL1 | ENST00000299004.13 | c.*120C>T | downstream_gene_variant | 2 | ENSP00000299004.9 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 157 of the AMOTL1 protein (p.Arg157Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with AMOTL1-related conditions (PMID: 30375152, 36116699; Invitae). In at least one individual the variant was observed to be de novo. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.