rs140398667
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001614.5(ACTG1):c.267C>T(p.Thr89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )
Consequence
ACTG1
NM_001614.5 synonymous
NM_001614.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.106
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 17-81511999-G-A is Benign according to our data. Variant chr17-81511999-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.106 with no splicing effect.
BS2
?
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTG1 | NM_001614.5 | c.267C>T | p.Thr89= | synonymous_variant | 3/6 | ENST00000573283.7 | |
ACTG1 | NM_001199954.3 | c.267C>T | p.Thr89= | synonymous_variant | 3/6 | ||
ACTG1 | NR_037688.3 | n.339C>T | non_coding_transcript_exon_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTG1 | ENST00000573283.7 | c.267C>T | p.Thr89= | synonymous_variant | 3/6 | 5 | NM_001614.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152244Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251256Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135890
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GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461744Hom.: 0 Cov.: 37 AF XY: 0.0000413 AC XY: 30AN XY: 727170
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74376
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 28, 2016 | p.Thr89Thr in Exon 03 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 3/6614 Finnish chrom osomes and 1/66206 European chromosomes by the Exome Aggregation Consortium (ExA C, http://exac.broadinstitute.org; dbSNP rs140398667). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 14, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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