rs397515724

Variant names:

• chrM-1119-T-C
• rs397515724
• ENST00000389680.2:n.472T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000389680.2(MT-RNR1):​n.472T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0053 (AC: 322)
• Consequence: MT-RNR1 ENST00000389680.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1 Possible-role-in-high-altitude-sickness
• Conservation: PhyloP100: -9.81
• Publications: 2 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 -10 ACMG points.

• BP6: Variant M-1119-T-C is Benign according to our data. Variant chrM-1119-T-C is described in ClinVar as Benign. ClinVar VariationId is 42209.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: High frequency in mitomap database: 0.0053
• BS2: High AC in GnomadMitoHomoplasmic at 40

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.472T>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.472T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

Mitomap GenBank AF: 0.0053 AC: 322

Gnomad homoplasmic AF: 0.00071 AC: 40 AN: 56427

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56427

Mitomap

Disease(s): Possible-role-in-high-altitude-sickness

Status: Reported

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 27, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.1119T>C in MTRNR1: This variant is not expected to have clinical significance because it has never been associated to hearing loss even though extensive study of this gene in hearing loss cases throughout the world and has been identified with similar frequencies among HL patients and controls (~1 - 5%) (Bae 2008, M utai 2011,Konings 2008, Lu 2010, Shen 2011). Also, this variant is common polymo rphism in phylogeny studies and belongs to one of the mitochondrial haplogroup s pecific variant (Kong 2006, Shen 2011). In addition, this variant is reported co mmonly in other general populations (LOVD database http://www.lovd.nl/2.0; mtDB http://www.mtdb.igp.uu.se; HmtDB http://www.hmtdb.uniba.it:8080/hmdb). Moreover, this region of mitochondrial DNA is not evolutionarily conserved (Lu 2010). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-9.8

Other links and lift over

dbSNP: rs397515724; hg19: chrM-1121;