chr11-66551645-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001104.4(ACTN3):c.380A>C(p.Glu127Ala) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001104.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN3 | NM_001104.4 | c.380A>C | p.Glu127Ala | missense_variant, splice_region_variant | 3/21 | ENST00000513398.2 | |
ACTN3 | NM_001258371.3 | c.509A>C | p.Glu170Ala | missense_variant, splice_region_variant | 3/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN3 | ENST00000513398.2 | c.380A>C | p.Glu127Ala | missense_variant, splice_region_variant | 3/21 | 1 | NM_001104.4 | P1 | |
ACTN3 | ENST00000502692.5 | c.509A>C | p.Glu170Ala | missense_variant, splice_region_variant | 3/21 | 2 | |||
ACTN3 | ENST00000511191.1 | c.*347A>C | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000879 AC: 22AN: 250366Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135726
GnomAD4 exome AF: 0.000140 AC: 205AN: 1461160Hom.: 0 Cov.: 33 AF XY: 0.000118 AC XY: 86AN XY: 726882
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74370
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2023 | The c.380A>C (p.E127A) alteration is located in exon 3 (coding exon 3) of the ACTN3 gene. This alteration results from a A to C substitution at nucleotide position 380, causing the glutamic acid (E) at amino acid position 127 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at