chr11-66551332-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_001104.4(ACTN3):c.241C>T(p.Leu81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00771 in 1,608,516 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0061 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0079 ( 59 hom. )
Consequence
ACTN3
NM_001104.4 synonymous
NM_001104.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.788
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP6
Variant 11-66551332-C-T is Benign according to our data. Variant chr11-66551332-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641991.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.788 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN3 | NM_001104.4 | c.241C>T | p.Leu81= | synonymous_variant | 2/21 | ENST00000513398.2 | |
ACTN3 | NM_001258371.3 | c.370C>T | p.Leu124= | synonymous_variant | 2/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN3 | ENST00000513398.2 | c.241C>T | p.Leu81= | synonymous_variant | 2/21 | 1 | NM_001104.4 | P1 | |
ACTN3 | ENST00000502692.5 | c.370C>T | p.Leu124= | synonymous_variant | 2/21 | 2 | |||
ACTN3 | ENST00000511191.1 | c.*208C>T | 3_prime_UTR_variant, NMD_transcript_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00607 AC: 924AN: 152204Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00619 AC: 1488AN: 240356Hom.: 12 AF XY: 0.00623 AC XY: 808AN XY: 129772
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GnomAD4 exome AF: 0.00788 AC: 11479AN: 1456194Hom.: 59 Cov.: 31 AF XY: 0.00779 AC XY: 5635AN XY: 723718
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GnomAD4 genome AF: 0.00607 AC: 924AN: 152322Hom.: 9 Cov.: 32 AF XY: 0.00581 AC XY: 433AN XY: 74484
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | ACTN3: BP4, BP7, BS2 - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at