7-19116735-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_000474.4(TWIST1):c.587G>A(p.Trp196*) variant causes a stop gained 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. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000474.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TWIST1 | ENST00000242261.6 | c.587G>A | p.Trp196* | stop_gained | Exon 1 of 2 | 1 | NM_000474.4 | ENSP00000242261.5 | ||
TWIST1 | ENST00000354571.5 | n.383G>A | non_coding_transcript_exon_variant | Exon 1 of 3 | 2 | ENSP00000346582.5 | ||||
TWIST1 | ENST00000443687.5 | n.188G>A | non_coding_transcript_exon_variant | Exon 1 of 4 | 4 | ENSP00000416986.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Saethre-Chotzen syndrome;C4551902:TWIST1-related craniosynostosis Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TWIST1 are known to be pathogenic (PMID: 10749989). This variant has been observed in individual(s) with craniosynostosis (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp196*) in the TWIST1 gene. It is expected to result in an absent or disrupted protein product. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.