rs727502884
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_001614.5(ACTG1):c.333C>T(p.Asn111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,128 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
ACTG1
NM_001614.5 synonymous
NM_001614.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.66
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 -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 17-81511933-G-A is Benign according to our data. Variant chr17-81511933-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 162719.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511933-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=2.66 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTG1 | NM_001614.5 | c.333C>T | p.Asn111= | synonymous_variant | 3/6 | ENST00000573283.7 | |
ACTG1 | NM_001199954.3 | c.333C>T | p.Asn111= | synonymous_variant | 3/6 | ||
ACTG1 | NR_037688.3 | n.405C>T | non_coding_transcript_exon_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTG1 | ENST00000573283.7 | c.333C>T | p.Asn111= | synonymous_variant | 3/6 | 5 | NM_001614.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250426Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135778
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461762Hom.: 0 Cov.: 37 AF XY: 0.00000688 AC XY: 5AN XY: 727178
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GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152366Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74514
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
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 | Jun 02, 2013 | Asn111Asn in exon 3 of ACTG1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located near a splice site. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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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