rs1428585182

Variant names:

• chr9-35657866-T-C
• rs1428585182
• ENST00000363046.2:n.154A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-35657866-T-C
• chr9-35657866-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000363046.2(RMRP):​n.154A>G variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000183 in 546,578 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 (★★).

• 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, multiple submitters, no conflicts U:4
• Conservation: PhyloP100: 7.13
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMRP	NR_003051.4	MANE Select	n.154A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMRP	ENST00000363046.2	TSL:6 MANE Select	n.154A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000183 AC: 1 AN: 546578 Hom.: 0 Cov.: 0 AF XY: 0.00000338 AC XY: 1 AN XY: 296106

African (AFR) AF: 0.00 AC: 0 AN: 14826

American (AMR) AF: 0.00 AC: 0 AN: 34586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19958

East Asian (EAS) AF: 0.00 AC: 0 AN: 32104

South Asian (SAS) AF: 0.00 AC: 0 AN: 62676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2428

European-Non Finnish (NFE) AF: 0.00000316 AC: 1 AN: 316638

Other (OTH) AF: 0.00 AC: 0 AN: 30170

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Metaphyseal chondrodysplasia, McKusick type Uncertain:1

Apr 17, 2017

Counsyl

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

Anauxetic dysplasia Uncertain:1

Sep 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 individual(s) with cartilage-hair hypoplasia (PMID: 12107819). This variant is also known as 152G. ClinVar contains an entry for this variant (Variation ID: 551539). 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.

Metaphyseal chondrodysplasia, McKusick type;C1834821:Metaphyseal dysplasia without hypotrichosis;C4551965:Anauxetic dysplasia 1 Uncertain:1

Oct 07, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Uncertain:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RMRP: PM2, PM3

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.75
PhyloP100		7.1
PromoterAI		-0.016	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1428585182; hg19: chr9-35657863;