rs121909189
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_000474.4(TWIST1):c.392T>C(p.Leu131Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L131Q) has been classified as Pathogenic.
Frequency
Consequence
NM_000474.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TWIST1 | NM_000474.4 | c.392T>C | p.Leu131Pro | missense_variant | 1/2 | ENST00000242261.6 | |
TWIST1 | NR_149001.2 | n.707T>C | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TWIST1 | ENST00000242261.6 | c.392T>C | p.Leu131Pro | missense_variant | 1/2 | 1 | NM_000474.4 | P1 | |
TWIST1 | ENST00000354571.5 | c.191T>C | p.Leu64Pro | missense_variant, NMD_transcript_variant | 1/3 | 2 | |||
TWIST1 | ENST00000443687.5 | upstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Saethre-Chotzen syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 26, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at