rs199701329
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001369268.1(ACAN):c.230G>A(p.Arg77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,614,026 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R77C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001369268.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACAN | NM_001369268.1 | c.230G>A | p.Arg77His | missense_variant | 3/19 | ENST00000560601.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACAN | ENST00000560601.4 | c.230G>A | p.Arg77His | missense_variant | 3/19 | 3 | NM_001369268.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00135 AC: 205AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00154 AC: 385AN: 249238Hom.: 1 AF XY: 0.00162 AC XY: 219AN XY: 135230
GnomAD4 exome AF: 0.00134 AC: 1962AN: 1461706Hom.: 1 Cov.: 32 AF XY: 0.00131 AC XY: 954AN XY: 727136
GnomAD4 genome ? AF: 0.00135 AC: 205AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.00158 AC XY: 118AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 15, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 11, 2023 | The c.230G>A (p.R77H) alteration is located in exon 3 (coding exon 2) of the ACAN gene. This alteration results from a G to A substitution at nucleotide position 230, causing the arginine (R) at amino acid position 77 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
ACAN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 02, 2019 | 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). - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Osteochondritis dissecans Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at