chr7-19117047-C-CCGCCGCCGCCGCCCGCGCCGCCGCCGCCCG
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM1
The NM_000474.4(TWIST1):c.274_275insCGGGCGGCGGCGGCGCGGGCGGCGGCGGCG(p.Gly91_Gly92insAlaGlyGlyGlyGlyAlaGlyGlyGlyGly) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_000474.4 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
Publications
- Saethre-Chotzen syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, PanelApp Australia, Laboratory for Molecular Medicine, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
- TWIST1-related craniosynostosisInheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
- isolated brachycephalyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- isolated plagiocephalyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- isolated scaphocephalyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Sweeney-Cox syndromeInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TWIST1 | NM_000474.4 | c.274_275insCGGGCGGCGGCGGCGCGGGCGGCGGCGGCG | p.Gly91_Gly92insAlaGlyGlyGlyGlyAlaGlyGlyGlyGly | conservative_inframe_insertion | Exon 1 of 2 | ENST00000242261.6 | NP_000465.1 | |
TWIST1 | NR_149001.2 | n.589_590insCGGGCGGCGGCGGCGCGGGCGGCGGCGGCG | non_coding_transcript_exon_variant | Exon 1 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TWIST1 | ENST00000242261.6 | c.274_275insCGGGCGGCGGCGGCGCGGGCGGCGGCGGCG | p.Gly91_Gly92insAlaGlyGlyGlyGlyAlaGlyGlyGlyGly | conservative_inframe_insertion | Exon 1 of 2 | 1 | NM_000474.4 | ENSP00000242261.5 | ||
TWIST1 | ENST00000354571.5 | n.70_71insCGGGCGGCGGCGGCGCGGGCGGCGGCGGCG | non_coding_transcript_exon_variant | Exon 1 of 3 | 2 | ENSP00000346582.5 | ||||
TWIST1 | ENST00000443687.5 | n.-126_-125insCGGGCGGCGGCGGCGCGGGCGGCGGCGGCG | upstream_gene_variant | 4 | ENSP00000416986.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at