rs1554651396

Variant names:

• chr9-35658018-C-CACGTCCTCAGCTTCACAG
• rs1554651396
• ENST00000363046.2:n.1_2insCTGTGAAGCTGAGGACGT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP5_Moderate

The NR_003051.4(RMRP):​n.1_2insCTGTGAAGCTGAGGACGT 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 0.00000558 in 537,988 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: RMRP NR_003051.4 non_coding_transcript_exon
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: -5.45
• 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: G2P, ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP5: Variant 9-35658018-C-CACGTCCTCAGCTTCACAG is Pathogenic according to our data. Variant chr9-35658018-C-CACGTCCTCAGCTTCACAG is described in ClinVar as Pathogenic. ClinVar VariationId is 552761.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_003051.4. 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.1_2insCTGTGAAGCTGAGGACGT		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.1_2insCTGTGAAGCTGAGGACGT		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000156 AC: 2 AN: 127922 AF XY: 0.0000143

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000558 AC: 3 AN: 537988 Hom.: 0 Cov.: 0 AF XY: 0.00000690 AC XY: 2 AN XY: 289814

African (AFR) AF: 0.00 AC: 0 AN: 15522

American (AMR) AF: 0.00 AC: 0 AN: 34330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19766

East Asian (EAS) AF: 0.00 AC: 0 AN: 31786

South Asian (SAS) AF: 0.0000481 AC: 3 AN: 62342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2408

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 308820

Other (OTH) AF: 0.00 AC: 0 AN: 29930

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Anauxetic dysplasia (1)
1	-	-	Metaphyseal chondrodysplasia, McKusick type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-5.5

Splicing

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

Other links and lift over

dbSNP: rs1554651396; hg19: chr9-35658015;