rs1554651251

chr9-35657947-T-Cchr9-35657947-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NR_003051.3(RMRP):n.72A>G variant causes a non coding transcript exon change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: RMRP NR_003051.3 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RMRP	NR_003051.3	n.72A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMRP	ENST00000363046.1	n.71A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000766 AC: 1 AN: 130488 Hom.: 0 AF XY: 0.0000140 AC XY: 1 AN XY: 71222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000447

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000912 AC: 5 AN: 548098 Hom.: 0 Cov.: 0 AF XY: 0.0000101 AC XY: 3 AN XY: 296796

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000160

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Metaphyseal chondrodysplasia, McKusick type Uncertain:2

Uncertain significance, no assertion criteria provided	clinical testing	Natera, Inc.	Jul 13, 2021	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Counsyl	Jun 16, 2017	- -

Anauxetic dysplasia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 27, 2021

This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in individual(s) with cartilage-hair hypoplasia (PMID: 26915675). This variant is also known as c.7A>G. ClinVar contains an entry for this variant (Variation ID: 552366). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
Cadd	Benign	20
Dann	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1554651251; hg19: chr9-35657944;