rs727504555

Variant names:

• chrM-1027-A-G
• rs727504555
• ENST00000389680.2:n.380A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

This summary comes from the ClinGen Evidence Repository: The m.1027A>G variant in MT-RNR1 has been reported in six unrelated individuals with primary mitochondrial disease. All had hearing loss (4/6 had aminoglycoside exposure; PMIDs: 21205314, 20100600). The variant was present at homoplasmy in both affected and unaffected individuals from these families. There are no de novo occurrences of this variant to our knowledge. This variant is present in population databases (MITOMAP: 0.028%; gnomAD v3.1.2: 0.025%; Helix: 0.037%). There are no in silico predictors for this type of variant in mitochondrial DNA. There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on August 12, 2024. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID:32906214): None. LINK:https://erepo.genome.network/evrepo/ui/classification/CA273573/MONDO:0044970/015

• Frequency: Mitomap GenBank: 𝑓 0.00030 (AC: 18)
• Consequence: RNR1 unassigned_transcript_4785 non_coding_transcript_exon
• Clinical Significance: Uncertain significance reviewed by expert panel P:1 U:1 DEAF-associated
• Conservation: PhyloP100: 1.04
• 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]

MT-RNR1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000389680.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-RNR1	ENST00000389680.2	TSL:6	n.380A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

Mitomap GenBank AF: 0.00030 AC: 18

Gnomad homoplasmic AF: 0.00025 AC: 14 AN: 56428

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56428

Mitomap

Disease(s): DEAF-associated

Status: Reported

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	1	-	Mitochondrial disease (1)
1	-	-	Rare genetic deafness (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

Other links and lift over

dbSNP: rs727504555; hg19: chrM-1029;