rs769080777

Variant names:

• chr9-35657758-C-A
• rs769080777
• ENST00000363046.2:n.262G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-35657758-C-A
• chr9-35657758-C-G
• chr9-35657758-C-T

Variant summary

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

The ENST00000363046.2(RMRP):​n.262G>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 0.00000561 in 534,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: RMRP ENST00000363046.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMRP	NR_003051.4	n.262G>T		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMRP	ENST00000363046.2	n.262G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000801 AC: 1 AN: 124812 AF XY: 0.00

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: 0.00000561 AC: 3 AN: 534446 Hom.: 0 Cov.: 0 AF XY: 0.00000348 AC XY: 1 AN XY: 287472

African (AFR) AF: 0.00 AC: 0 AN: 15500

American (AMR) AF: 0.00 AC: 0 AN: 34096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19552

East Asian (EAS) AF: 0.00 AC: 0 AN: 31826

South Asian (SAS) AF: 0.0000484 AC: 3 AN: 61986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2398

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 306468

Other (OTH) AF: 0.00 AC: 0 AN: 29712

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	9.0
DANN	Benign	0.91
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs769080777; hg19: chr9-35657755;