9-35657838-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NR_003051.4(RMRP):n.182G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000721 in 693,312 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 (★).
Frequency
Consequence
NR_003051.4 non_coding_transcript_exon
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RMRP | NR_003051.4 | n.182G>C | non_coding_transcript_exon_variant | Exon 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RMRP | ENST00000363046.1 | n.180G>C | non_coding_transcript_exon_variant | Exon 1 of 1 | 6 |
Frequencies
GnomAD3 genomes AF: 0.00000688 AC: 1AN: 145276Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000768 AC: 1AN: 130180Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 71116
GnomAD4 exome AF: 0.00000730 AC: 4AN: 548036Hom.: 0 Cov.: 0 AF XY: 0.00000337 AC XY: 1AN XY: 296766
GnomAD4 genome AF: 0.00000688 AC: 1AN: 145276Hom.: 0 Cov.: 33 AF XY: 0.0000141 AC XY: 1AN XY: 71062
ClinVar
Submissions by phenotype
Anauxetic dysplasia Uncertain:1
This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has been observed in individual(s) with clincial features of cartilage-hair hypoplasia anauxetic dysplasia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 465203). This variant disrupts the n.181G nucleotide in the RMRP gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 16254002, 16838329, 27862957). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. 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