chr11-66546753-C-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001258371.3(ACTN3):c.243C>G(p.Pro81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,535,636 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0088 ( 21 hom., cov: 32)
Exomes 𝑓: 0.00092 ( 20 hom. )
Consequence
ACTN3
NM_001258371.3 synonymous
NM_001258371.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.282
Genes affected
ACTN3 (HGNC:165): (actinin alpha 3) This gene encodes a member of the alpha-actin binding protein gene family. The encoded protein is primarily expressed in skeletal muscle and functions as a structural component of sarcomeric Z line. This protein is involved in crosslinking actin containing thin filaments. An allelic polymorphism in this gene results in both coding and non-coding variants; the reference genome represents the coding allele. The non-functional allele of this gene is associated with elite athlete status. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 11-66546753-C-G is Benign according to our data. Variant chr11-66546753-C-G is described in ClinVar as [Benign]. Clinvar id is 3050805.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.282 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00876 (1334/152208) while in subpopulation AFR AF= 0.0299 (1242/41522). AF 95% confidence interval is 0.0285. There are 21 homozygotes in gnomad4. There are 596 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN3 | NM_001258371.3 | c.243C>G | p.Pro81= | synonymous_variant | 1/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN3 | ENST00000502692.5 | c.243C>G | p.Pro81= | synonymous_variant | 1/21 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00875 AC: 1331AN: 152090Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.00206 AC: 277AN: 134650Hom.: 5 AF XY: 0.00132 AC XY: 97AN XY: 73404
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GnomAD4 exome AF: 0.000921 AC: 1274AN: 1383428Hom.: 20 Cov.: 32 AF XY: 0.000769 AC XY: 525AN XY: 682602
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GnomAD4 genome ? AF: 0.00876 AC: 1334AN: 152208Hom.: 21 Cov.: 32 AF XY: 0.00801 AC XY: 596AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ACTN3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 26, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at