M-955-A-AC

Variant names:

• chrM-955-A-AC
• rs111033185
• unassigned_transcript_4785:n.313dupC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0063 (AC: 388)
• Consequence: RNR1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1 Possibly-DEAF-associated
• Conservation: PhyloP100: -5.51

Genes affected

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 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_single_submitter, 1 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

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0063 AC: 388

Mitomap

Possibly-DEAF-associated

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111033185; hg19: chrM-957;