rs193117694

chr9-35657965-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NR_003051.3(RMRP):n.54C>T 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 0.00352 in 700,470 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (3 hom., cov: 34)
  • Exomes 𝑓: 0.0037 (7 hom.)
• Consequence: RMRP NR_003051.3 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.26

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 9-35657965-G-A is Benign according to our data. Variant chr9-35657965-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-35657965-G-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RMRP	NR_003051.3	n.54C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMRP	ENST00000363046.1	n.53C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 453 AN: 152254 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00523

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00290 AC: 379 AN: 130476 Hom.: 0 AF XY: 0.00295 AC XY: 210 AN XY: 71210

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00218

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00134

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.00541

Gnomad OTH exome AF: 0.00349

GnomAD4 exome AF: 0.00368 AC: 2015 AN: 548098 Hom.: 7 Cov.: 0 AF XY: 0.00356 AC XY: 1056 AN XY: 296798

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.00228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00137

Gnomad4 FIN exome AF: 0.000422

Gnomad4 NFE exome AF: 0.00537

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.00297 AC: 453 AN: 152372 Hom.: 3 Cov.: 34 AF XY: 0.00279 AC XY: 208 AN XY: 74522

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00523

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00367 Hom.: 1

Bravo AF: 0.00328

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	RMRP: BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Anauxetic dysplasia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

RMRP-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 17, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.070
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs193117694; hg19: chr9-35657962;