chr11-66546977-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001104.4(ACTN3):c.40G>A(p.Glu14Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000328 in 1,524,418 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E14A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001104.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN3 | NM_001104.4 | c.40G>A | p.Glu14Lys | missense_variant | 1/21 | ENST00000513398.2 | |
ACTN3 | NM_001258371.3 | c.276+191G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN3 | ENST00000513398.2 | c.40G>A | p.Glu14Lys | missense_variant | 1/21 | 1 | NM_001104.4 | P1 | |
ACTN3 | ENST00000502692.5 | c.276+191G>A | intron_variant | 2 | |||||
ACTN3 | ENST00000511191.1 | c.40G>A | p.Glu14Lys | missense_variant, NMD_transcript_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000146 AC: 2AN: 1372194Hom.: 0 Cov.: 32 AF XY: 0.00000297 AC XY: 2AN XY: 674036
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74372
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 03, 2023 | The c.40G>A (p.E14K) 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 40, causing the glutamic acid (E) at amino acid position 14 to be replaced by a lysine (K). 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