M-827-A-G

Variant names:

• chrM-827-A-G
• rs28358569
• ENST00000389680.2:n.180A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000000000(RNR1):​n.180A>G variant causes a non coding transcript exon change. Variant has been reported in ClinVar as drug response (★).

• Frequency: Mitomap GenBank: 𝑓 0.026 (AC: 1585)
• Consequence: RNR1 ENST00000000000 non_coding_transcript_exon
• Clinical Significance: drug response criteria provided, single submitter P:2 O:1 DEAF
• Conservation: PhyloP100: 4.81
• Publications: 10 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]

TRNF (HGNC:7481): (mitochondrially encoded tRNA phenylalanine)

TRNF Gene-Disease associations (from GenCC):

• mitochondrial disease

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

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: High frequency in mitomap database: 0.025899999

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.180A>G		non_coding_transcript_exon_variant	Exon 1 of 1
TRNF	unassigned_transcript_4784	c.*180A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.180A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TF	ENST00000387314.1	n.*180A>G		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.026 AC: 1585

Gnomad homoplasmic AF: 0.023 AC: 1309 AN: 56404

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56404

Alfa AF: 0.0296 Hom.: 347

Mitomap

Disease(s): DEAF

Status: Conflicting-reports

ClinVar

Significance: drug response

Submissions summary: Pathogenic:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial non-syndromic sensorineural hearing loss Pathogenic:1

Apr 11, 2008

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Aminoglycoside-induced deafness Pathogenic:1

Apr 11, 2008

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Gentamicin response Other:1

Aug 01, 2018

Medical Genetics Summaries

Significance: drug response

Review Status: criteria provided, single submitter

Collection Method: curation

The m.827A>G variant has been associated with non-syndromic hearing loss, both with and without the use of aminoglycosides. Adverse effect: Gentamicin-induced hearing loss

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8
Mutation Taster		=65/35	polymorphism

Other links and lift over

dbSNP: rs28358569; hg19: chrM-829;