chrM-1415-G-A

Variant names:

• chrM-1415-G-A
• rs876657505
• ENST00000389680.2:n.768G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000389680.2(MT-RNR1):​n.768G>A 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 0.0011 (AC: 66)
• Consequence: MT-RNR1 ENST00000389680.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.50
• Publications: 0 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]

TRNV (HGNC:7500): (mitochondrially encoded tRNA valine)

TRNV Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• Leigh syndrome

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant M-1415-G-A is Benign according to our data. Variant chrM-1415-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 227549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 27

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.768G>A		non_coding_transcript_exon_variant	Exon 1 of 1
TRNV	unassigned_transcript_4786	c.-187G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.768G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TV	ENST00000387342.1	n.-187G>A		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0011 AC: 66

Gnomad homoplasmic AF: 0.00048 AC: 27 AN: 56417

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56417

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 26, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.1415G>A in MTRNR1: This variant is not expected to have clinical significance because it has been identified in several human phylogeny studies at an overall frequency of 0.1% (37/29867 human mitochondrial DNA sequences) with haplogroup-s pecific frequencies ranging from 0.1% to 66% (http://www.hmtdb.uniba.it:8080/hmd b/; http://www.mitomap.org; http://www.mtdb.igp.uu.se). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.5
Mutation Taster		=99/1	polymorphism

Other links and lift over

dbSNP: rs876657505; hg19: chrM-1417; COSMIC: COSV104421126;