chr11-66547080-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001104.4(ACTN3):c.143G>A(p.Arg48Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000085 in 1,505,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000093 ( 0 hom. )
Consequence
ACTN3
NM_001104.4 missense
NM_001104.4 missense
Scores
2
5
2
Clinical Significance
Conservation
PhyloP100: 7.17
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN3 | NM_001104.4 | c.143G>A | p.Arg48Gln | missense_variant | 1/21 | ENST00000513398.2 | |
ACTN3 | NM_001258371.3 | c.276+294G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN3 | ENST00000513398.2 | c.143G>A | p.Arg48Gln | missense_variant | 1/21 | 1 | NM_001104.4 | P1 | |
ACTN3 | ENST00000502692.5 | c.276+294G>A | intron_variant | 2 | |||||
ACTN3 | ENST00000511191.1 | c.143G>A | p.Arg48Gln | missense_variant, NMD_transcript_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152238Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000931 AC: 126AN: 1352826Hom.: 0 Cov.: 32 AF XY: 0.0000968 AC XY: 64AN XY: 661424
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74382
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2023 | The c.143G>A (p.R48Q) alteration is located in exon 1 (coding exon 1) of the ACTN3 gene. This alteration results from a G to A substitution at nucleotide position 143, causing the arginine (R) at amino acid position 48 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
MetaRNN
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
GERP RS
Varity_R
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