14-68875002-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001130004.2(ACTN1):c.2602G>A(p.Asp868Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,522 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. D868G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130004.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN1 | NM_001130004.2 | c.2602G>A | p.Asp868Asn | missense_variant | 22/22 | ENST00000394419.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN1 | ENST00000394419.9 | c.2602G>A | p.Asp868Asn | missense_variant | 22/22 | 1 | NM_001130004.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249444Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135340
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461180Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726914
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 868 of the ACTN1 protein (p.Asp868Asn). This variant is present in population databases (rs199707794, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ACTN1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at