ENST00000363046.2:n.250C>T

Variant names:

• chr9-35657770-G-A
• rs1554651104
• ENST00000363046.2:n.250C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000363046.2(RMRP):​n.250C>T variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 543,104 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 (★). The gene RMRP is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: RMRP ENST00000363046.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 8.94
• Publications: 0 publications found

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]

RMRP Gene-Disease associations (from GenCC):

• cartilage-hair hypoplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Myriad Women's Health

ACMG classification

Specifications for RMRP are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000363046.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMRP	NR_003051.4	MANE Select	n.250C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMRP	ENST00000363046.2	TSL:6 MANE Select	n.250C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000184 AC: 1 AN: 543104 Hom.: 0 Cov.: 0 AF XY: 0.00000341 AC XY: 1 AN XY: 293258

African (AFR) AF: 0.00 AC: 0 AN: 15662

American (AMR) AF: 0.00 AC: 0 AN: 34592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19904

East Asian (EAS) AF: 0.00 AC: 0 AN: 31986

South Asian (SAS) AF: 0.00 AC: 0 AN: 62538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2424

European-Non Finnish (NFE) AF: 0.00000320 AC: 1 AN: 312744

Other (OTH) AF: 0.00 AC: 0 AN: 30184

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Metaphyseal chondrodysplasia, McKusick type (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Benign	0.97
PhyloP100		8.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1554651104;

hg19: chr9-35657767;