14-68874992-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_001130004.2(ACTN1):c.2612G>A(p.Arg871His) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,613,584 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R871C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130004.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN1 | NM_001130004.2 | c.2612G>A | p.Arg871His | missense_variant | 22/22 | ENST00000394419.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN1 | ENST00000394419.9 | c.2612G>A | p.Arg871His | missense_variant | 22/22 | 1 | NM_001130004.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000250 AC: 38AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000841 AC: 21AN: 249688Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135420
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461272Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 726956
GnomAD4 genome ? AF: 0.000249 AC: 38AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 2017 | The R871H variant in the ACTN1 gene has not been reported previously as a germline pathogenic variant, nor as a benign variant, to our knowledge. The R871H variant is observed in 9/9776 (0.09%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R871H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R871H as a variant of uncertain significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 2022 | - - |
ACTN1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 13, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at