rs1555419008
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_005159.5(ACTC1):c.69T>G(p.Phe23Leu) variant causes a missense change involving the alteration of a non-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 Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar.
Frequency
Consequence
NM_005159.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTC1 | NM_005159.5 | c.69T>G | p.Phe23Leu | missense_variant | 2/7 | ENST00000290378.6 | |
GJD2-DT | NR_120329.1 | n.300-15756A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTC1 | ENST00000290378.6 | c.69T>G | p.Phe23Leu | missense_variant | 2/7 | 1 | NM_005159.5 | P1 | |
GJD2-DT | ENST00000671663.1 | n.95-15756A>C | intron_variant, non_coding_transcript_variant | ||||||
ACTC1 | ENST00000560563.2 | n.175T>G | non_coding_transcript_exon_variant | 2/6 | 2 | ||||
GJD2-DT | ENST00000503496.6 | n.300-15756A>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 21, 2022 | The p.F23L variant (also known as c.69T>G), located in coding exon 1 of the ACTC1 gene, results from a T to G substitution at nucleotide position 69. The phenylalanine at codon 23 is replaced by leucine, an amino acid with highly similar properties. A different alteration located at the same position, resulting in the same protein change, c.67T>C p.F23L, was observed in two individuals reported to have hypertrophic cardiomyopathy; however, clinical details were limited (Coppini R et al. J Am Coll Cardiol. 2014;64:2589-600). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at