rs1556422511

Variant names:

• chrM-1183-T-C
• rs1556422511
• ENST00000389680.2:n.536T>C

Variant summary

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

The ENST00000389680.2(MT-RNR1):​n.536T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 4)
• Consequence: MT-RNR1 ENST00000389680.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.729
• Publications: 0 publications found

Genes affected

MT-RNR1 (HGNC:7470): (mitochondrially encoded 12S RNA) Enables DNA binding activity and DNA-binding transcription factor binding activity. Involved in several processes, including osteoblast proliferation; regulation of carbohydrate utilization; and regulation of phosphate metabolic process. Located in extracellular space; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.536T>C		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.536T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

Mitomap GenBank AF: 0.00010 AC: 4

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 06, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant classified as Uncertain Significance - Favor Benign. The m.1183T>C varia nt in MT-RNR1 has not been previously reported in individuals with hearing loss, but has been identified in 0.1% (1/698) of human mitochondrial DNA sequences of the haplogroup L2a, which is of African origin (http://www.mitomap.org). Howeve r, this frequency is not high enough to rule out a pathogenic role. The thymine (T) nucleotide at position m.1183 is conserved in mammals, but is not conserved in birds or fish, suggesting that a change at this position may be tolerated. Ho wever, this information is not predictive enough to rule out pathogenicity. In s ummary, while the clinical significance of the m.1183T>C variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.73

Other links and lift over

dbSNP: rs1556422511; hg19: chrM-1185;