rs587779771
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PP2PP3_StrongPP5_Moderate
The NM_001101.5(ACTB):c.224T>C(p.Ile75Thr) 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. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I75M) has been classified as Uncertain significance.
Frequency
Consequence
NM_001101.5 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 |
---|---|---|---|---|---|---|---|
ACTB | NM_001101.5 | c.224T>C | p.Ile75Thr | missense_variant | 3/6 | ENST00000646664.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTB | ENST00000646664.1 | c.224T>C | p.Ile75Thr | missense_variant | 3/6 | NM_001101.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Baraitser-Winter syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Department of Genetics, Robert DEBRE University Hospital | Apr 15, 2014 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 19, 2017 | The I75T variant in the ACTB gene has been reported previously in association with Baraitser-Winter cerebrofrontofacial syndrome (Verloes et al., 2015a). The I75T variant is not observed in large population cohorts (Lek et al., 2016). The I75T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret I75T as a likely pathogenic variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at