chrM-955-A-AC

Variant names:

• chrM-955-A-AC
• rs111033185
• ENST00000389680.2:n.313dupC

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The ENST00000000000(RNR1):​n.313dupC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0063 (AC: 388)
• Consequence: RNR1 ENST00000000000 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 Possibly-DEAF-associated
• Conservation: PhyloP100: -5.51
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP6: Variant M-955-A-AC is Benign according to our data. Variant chrM-955-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 42234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: High frequency in mitomap database: 0.0063

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.313dupC		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.313dupC		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

Mitomap GenBank AF: 0.0063 AC: 388

Mitomap

Disease(s): Possibly-DEAF-associated

Status: Reported

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 17, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.960_961insC variant in MTRNR1: This variant has been proposed to contribute to hearing loss when found in combination with a second known pathogenic mutation in the MTRNR1 gene (Li 2004, Zhao 2004). It has also been identified in >1% indi viduals without hearing loss (Pulkes 2003, Tang 2002, Zhao 2004). Studies have r evealed that these variants are present in similar frequencies among HL patients and normal hearing controls and that they are part of a common Asian haplogroup (Yao 2006, Bae 2008, Tanaka 2010, Shen 2011), and the variant is present at hig h frequency in several haplogroups ranging from 0.1% to 75% in the MitoMap datab ase (http://www.mitomap.org/MITOMAP). Moreover, this region of mitochondrial DN A is not evolutionarily conserved and its function is not well defined (Guan 201 1). In summary, there is insufficient evidence to support a disease-associated r ole or risk for ototoxicity of this variant alone and the population frequency o f the variant suggests that it is most likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-5.5

Other links and lift over

dbSNP: rs111033185; hg19: chrM-957;