rs1139406
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001614.5(ACTG1):āc.1026T>Cā(p.Gly342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,612,654 control chromosomes in the GnomAD database, including 637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.041 ( 222 hom., cov: 32)
Exomes š: 0.017 ( 415 hom. )
Consequence
ACTG1
NM_001614.5 synonymous
NM_001614.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.01
Genes affected
ACTG1 (HGNC:144): (actin gamma 1) Actins are highly conserved proteins that are involved in various types of cell motility and in maintenance of the cytoskeleton. Three main groups of actin isoforms have been identified in vertebrate animals: alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. Actin gamma 1, encoded by this gene, is a cytoplasmic actin found in all cell types. Mutations in this gene are associated with DFNA20/26, a subtype of autosomal dominant non-syndromic sensorineural progressive hearing loss and also with Baraitser-Winter syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 17-81510792-A-G is Benign according to our data. Variant chr17-81510792-A-G is described in ClinVar as [Benign]. Clinvar id is 128268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81510792-A-G is described in Lovd as [Likely_benign]. Variant chr17-81510792-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-3.01 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTG1 | NM_001614.5 | c.1026T>C | p.Gly342= | synonymous_variant | 6/6 | ENST00000573283.7 | |
ACTG1 | NM_001199954.3 | c.1026T>C | p.Gly342= | synonymous_variant | 6/6 | ||
ACTG1 | NR_037688.3 | n.1098T>C | non_coding_transcript_exon_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTG1 | ENST00000573283.7 | c.1026T>C | p.Gly342= | synonymous_variant | 6/6 | 5 | NM_001614.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0405 AC: 6115AN: 150880Hom.: 224 Cov.: 32
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GnomAD3 exomes AF: 0.0225 AC: 5645AN: 251294Hom.: 138 AF XY: 0.0208 AC XY: 2824AN XY: 135874
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GnomAD4 exome AF: 0.0165 AC: 24137AN: 1461654Hom.: 415 Cov.: 30 AF XY: 0.0163 AC XY: 11845AN XY: 727138
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GnomAD4 genome ? AF: 0.0406 AC: 6124AN: 151000Hom.: 222 Cov.: 32 AF XY: 0.0402 AC XY: 2965AN XY: 73820
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 13, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 20, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Gly342Gly in Exon 06 of ACTG1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 8.3% (311/3738) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs1139406). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 23, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Autosomal dominant nonsyndromic hearing loss 20 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Autosomal dominant nonsyndromic hearing loss 20;C3281235:Baraitser-winter syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Baraitser-winter syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at