M-961-T-G

Variant names:

• chrM-961-T-G
• rs3888511
• unassigned_transcript_4785:n.314T>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

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

• Frequency: Mitomap GenBank: 𝑓 0.0037 (AC: 226)
• Consequence: RNR1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter P:1 U:1 B:1 DEAF+-possibly-LVNC-associated,DEAF-/-AD-associated-/-intellectual-disability,Possibly-DEAF-associated
• Conservation: PhyloP100: -7.53

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-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_single_submitter, 1 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

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0037 AC: 226

Gnomad homoplasmic AF: 0.0078 AC: 442 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Mitomap

DEAF+-possibly-LVNC-associated,DEAF-/-AD-associated-/-intellectual-disability,Possibly-DEAF-associated

ClinVar

Significance: Likely benign

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

Revision: criteria provided, single submitter

Submissions by phenotype

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

Jun 14, 2018

GeneReviews

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Aug 01, 2004

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not specified Benign:1

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. -

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: rs3888511; hg19: chrM-963;