NM_000047.3:c.36G>C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3BS1_SupportingBS2
The NM_000047.3(ARSL):c.36G>C(p.Arg12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000826 in 1,210,446 control chromosomes in the GnomAD database, including 1 homozygotes. There are 29 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000047.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000356 AC: 4AN: 112386Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34552
GnomAD3 exomes AF: 0.0000711 AC: 13AN: 182799Hom.: 0 AF XY: 0.0000595 AC XY: 4AN XY: 67263
GnomAD4 exome AF: 0.0000874 AC: 96AN: 1098060Hom.: 1 Cov.: 31 AF XY: 0.0000770 AC XY: 28AN XY: 363416
GnomAD4 genome AF: 0.0000356 AC: 4AN: 112386Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34552
ClinVar
Submissions by phenotype
X-linked chondrodysplasia punctata 1 Pathogenic:1Uncertain:1
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Chondrodysplasia punctata, brachytelephalangic, autosomal Uncertain:1
This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 12 of the ARSE protein (p.Arg12Ser). This variant is present in population databases (rs122460151, gnomAD 0.02%). This missense change has been observed in individual(s) with chondrodysplasia punctata (PMID: 7720070). ClinVar contains an entry for this variant (Variation ID: 11522). 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. Experimental studies have shown that this missense change does not substantially affect ARSE function (PMID: 9497243). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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