M-961-T-G

Variant names:

• chrM-961-T-G
• rs3888511
• ENST00000389680.2:n.314T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000000000(RNR1):​n.314T>G 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 0.0037 (AC: 226)
• Consequence: RNR1 ENST00000000000 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts P:1 U:1 B:2 DEAF+-possibly-LVNC-associated,DEAF-/-AD-associated-/-intellectual-disability,Possibly-DEAF-associated
• Conservation: PhyloP100: -7.53
• Publications: 13 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-961-T-G is Benign according to our data. Variant chrM-961-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 9633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 442

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.314T>G		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.314T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

Mitomap GenBank AF: 0.0037 AC: 226

Gnomad homoplasmic AF: 0.0078 AC: 442 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Mitomap

Disease(s): DEAF+-possibly-LVNC-associated,DEAF-/-AD-associated-/-intellectual-disability,Possibly-DEAF-associated

Status: Unclear,Unclear,Unclear

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1 Uncertain:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial non-syndromic sensorineural hearing loss Pathogenic:1 Uncertain:1

Aug 01, 2004

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jun 14, 2018

GeneReviews

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not specified Benign:2

Feb 06, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.961T>G in MTRNR1: This variant is not expected to have clinical significance b ecause it has been reported in phylogenetic studies with a haplogroup-specific f requency in central Europeans of 98% (http://mitomap.org/MITOMAP, http://www.mtd b.igp.uu.se). Several studies have associated this variant with maternally inher ited hearing loss (Li 2004, Yelverton 2013). However, other studies have identif ied this variant as common in the general population with similar frequencies am ong hearing loss patients and controls (0.2% ? 3%) (Bardien 2009, Elstner 2008, Konings 2008, Rydzanicz 2010; 6 observations in the LOVD database http://www.lov d.nl/2.0; 0.2% (5/2704) in mtDB http://www.mtdb.igp.uu.se; 1% in HmtDB http://ww w.hmtdb.uniba.it:8080/hmdb). In addition, in one study there was no difference o bserved in the mitochondrial translation products with the m.961T>G mutation com pared to controls (Elstner 2008). Moreover, this region of mitochondrial DNA is not evolutionarily conserved and its function is not well defined. Of note, chic ken has guanine at position m.961 (Konings 2008). One study of cystic fibrosis a dult patients did not observe a correlation between this variant and aminoglycos ide ototoxicity (Conrad 2008). In summary, the current data for this variant sup ports a likely benign role. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-7.5

Other links and lift over

dbSNP: rs3888511; hg19: chrM-963;