9-35657954-A-G

Variant names:

• chr9-35657954-A-G
• rs1357036842
• ENST00000363046.2:n.66T>C

Variant summary

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

The NR_003051.4(RMRP):​n.66T>C variant causes a non coding transcript exon change. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RMRP NR_003051.4 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.19
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).

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.66T>C		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.66T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 548102 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 296796

African (AFR) AF: 0.00 AC: 0 AN: 15734

American (AMR) AF: 0.00 AC: 0 AN: 34708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20026

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 62682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2444

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 316790

Other (OTH) AF: 0.00 AC: 0 AN: 30416

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Anauxetic dysplasia (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		5.2
PromoterAI		-0.023	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1357036842; hg19: chr9-35657951;