ENST00000389680.2:n.343T>C

Variant names:

• chrM-990-T-C
• rs727503165
• ENST00000389680.2:n.343T>C

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.343T>C 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 0.00060 (AC: 36)
• Consequence: MT-RNR1 ENST00000389680.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1 DEAF
• Conservation: PhyloP100: -0.650
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant M-990-T-C is Benign according to our data. Variant chrM-990-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 163989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 85

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.343T>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.343T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

Mitomap GenBank AF: 0.00060 AC: 36

Gnomad homoplasmic AF: 0.0015 AC: 85 AN: 56429

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56429

Mitomap

Disease(s): DEAF

Status: Reported

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 13, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.990T>C in MT-RNR1: The m.990T>C variant has been previously reported in 2/908 (0.2%) individuals with hearing loss and was not detected in 849 controls in tho se studies (Konings 2008, Shen 2011). However, it has been identified in 1.89% ( 19/1008) of individuals from broad populations by several human phylogeny studie s (MitoMap.org). Therefore, in the absence of any statistically significant asso ciation to hearing loss, the frequency of this variant in the general population , as evidenced by the phylogeny studies, suggests that it is likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.65

Other links and lift over

dbSNP: rs727503165; hg19: chrM-992;