rs727502882
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_Strong
The NM_001614.5(ACTG1):c.853T>C(p.Cys285Arg) 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. 12/19 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C285Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_001614.5 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 |
---|---|---|---|---|---|---|---|
ACTG1 | NM_001614.5 | c.853T>C | p.Cys285Arg | missense_variant | 5/6 | ENST00000573283.7 | |
ACTG1 | NM_001199954.3 | c.853T>C | p.Cys285Arg | missense_variant | 5/6 | ||
ACTG1 | NR_037688.3 | n.925T>C | non_coding_transcript_exon_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTG1 | ENST00000573283.7 | c.853T>C | p.Cys285Arg | missense_variant | 5/6 | 5 | NM_001614.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 38
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 11, 2013 | The Cys285Arg variant in ACTG1 has not been reported in individuals affected wit h hearing loss or in large population studies. Computational analyses (biochemic al amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that variant may impact the protein and the variant affects a conserved cysteine (Cys) residue which may alter the structure of the protein. However, this infor mation is not predictive enough to assume pathogenicity. In summary, additional studies are needed to fully assess the clinical significance of the Cys285Arg va riant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at