14-68874876-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM5PP2PP3
The NM_001130004.2(ACTN1):c.2728G>A(p.Gly910Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,588,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G910R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001130004.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN1 | NM_001130004.2 | c.2728G>A | p.Gly910Ser | missense_variant | 22/22 | ENST00000394419.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN1 | ENST00000394419.9 | c.2728G>A | p.Gly910Ser | missense_variant | 22/22 | 1 | NM_001130004.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152074Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000818 AC: 2AN: 244586Hom.: 0 AF XY: 0.00000756 AC XY: 1AN XY: 132250
GnomAD4 exome AF: 0.0000111 AC: 16AN: 1436594Hom.: 0 Cov.: 31 AF XY: 0.0000127 AC XY: 9AN XY: 709506
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74410
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with ACTN1-related conditions. This variant is present in population databases (rs192640536, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 910 of the ACTN1 protein (p.Gly910Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at