9-35657983-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NR_003051.4(RMRP):n.37C>G variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 700,436 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 Likely pathogenic (★).
Frequency
Consequence
NR_003051.4 non_coding_transcript_exon
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RMRP | NR_003051.4 | n.37C>G | 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.35C>G | non_coding_transcript_exon_variant | Exon 1 of 1 | 6 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000730 AC: 4AN: 548070Hom.: 0 Cov.: 0 AF XY: 0.0000101 AC XY: 3AN XY: 296786
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152366Hom.: 0 Cov.: 34 AF XY: 0.0000268 AC XY: 2AN XY: 74508
ClinVar
Submissions by phenotype
Anauxetic dysplasia Pathogenic:1
This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with RMRP-related conditions (PMID: 32021596). ClinVar contains an entry for this variant (Variation ID: 655898). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the n.36C nucleotide in the RMRP gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 16244706, 18164267). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Metaphyseal chondrodysplasia, McKusick type Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at