ENST00000389680.2:n.394A>G

Variant names:

• chrM-1041-A-G
• rs58327546
• ENST00000389680.2:n.394A>G

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.394A>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 0.0053 (AC: 327)
• 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: -3.88
• Publications: 3 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-1041-A-G is Benign according to our data. Variant chrM-1041-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 505132.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 21

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.394A>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.394A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

Mitomap GenBank AF: 0.0053 AC: 327

Gnomad homoplasmic AF: 0.00037 AC: 21 AN: 56431

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56431

Alfa AF: 0.00107 Hom.: 42

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 20, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.1041A>G in MTRNR1: This variant is not expected to have clinical significance because it has been identified in 0.6% (170/30589) human mitochondrial DNA seque nces with haplogroup-specific frequencies ranging from 0.01% to 0.9% in at leas t 5 haplogroups primarily of Asian descent (http://www.mitomap.org). In addition , while it has been reported in individuals with hearing loss, there was no diff erence between its frequency in patients versus controls (Liu 2010, Konings 2008 ). Therefore, this variant is likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.9

Other links and lift over

dbSNP: rs58327546; hg19: chrM-1043;