NM_001369268.1:c.230G>A
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).
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACAN | NM_001369268.1 | c.230G>A | p.Arg77His | missense_variant | Exon 3 of 19 | ENST00000560601.4 | NP_001356197.1 |
Ensembl
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
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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
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
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
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Osteochondritis dissecans Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at