rs387906533
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NR_003051.3(RMRP):n.91_92delinsGC variant causes a non coding transcript exon change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Consequence
RMRP
NR_003051.3 non_coding_transcript_exon
NR_003051.3 non_coding_transcript_exon
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.16
Genes affected
RMRP (HGNC:10031): (RNA component of mitochondrial RNA processing endoribonuclease) This gene encodes the RNA component of mitochondrial RNA processing endoribonuclease, which cleaves mitochondrial RNA at a priming site of mitochondrial DNA replication. This RNA also interacts with the telomerase reverse transcriptase catalytic subunit to form a distinct ribonucleoprotein complex that has RNA-dependent RNA polymerase activity and produces double-stranded RNAs that can be processed into small interfering RNA. Mutations in this gene are associated with cartilage-hair hypoplasia.[provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-35657927-CT-GC is Pathogenic according to our data. Variant chr9-35657927-CT-GC is described in ClinVar as [Pathogenic]. Clinvar id is 14227.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RMRP | NR_003051.3 | n.91_92delinsGC | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RMRP | ENST00000363046.1 | n.90_91delinsGC | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Anauxetic dysplasia 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2005 | - - |
Anauxetic dysplasia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 17, 2023 | This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has been observed in individual(s) with autosomal recessive anauxetic dysplasia (PMID: 16252239). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as _x0001_+90_91AG>GC. ClinVar contains an entry for this variant (Variation ID: 14227). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects RMRP function (PMID: 16252239, 17701897). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at