rs1553255301
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_ModeratePP5_Moderate
The NM_001100.4(ACTA1):c.1054T>C(p.Ser352Pro) 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S352F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001100.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTA1 | NM_001100.4 | c.1054T>C | p.Ser352Pro | missense_variant | 7/7 | ENST00000366684.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTA1 | ENST00000366684.7 | c.1054T>C | p.Ser352Pro | missense_variant | 7/7 | 1 | NM_001100.4 | P1 | |
ENST00000702606.1 | n.214A>G | non_coding_transcript_exon_variant | 1/1 | ||||||
ACTA1 | ENST00000684723.1 | c.919T>C | p.Ser307Pro | missense_variant | 6/6 | ||||
ACTA1 | ENST00000366683.4 | c.991-15T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Actin accumulation myopathy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACTA1 protein function. ClinVar contains an entry for this variant (Variation ID: 464113). This missense change has been observed in individual(s) with congenital myopathy (Invitae). In at least one individual the variant was observed to be de novo. This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 352 of the ACTA1 protein (p.Ser352Pro). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at