ENST00000389680.2:n.735A>C

Variant names:

• chrM-1382-A-C
• rs111033358
• ENST00000389680.2:n.735A>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.735A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0031 (AC: 192)
• Consequence: MT-RNR1 ENST00000389680.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1 Longevity-/-T2D-susceptibility
• Conservation: PhyloP100: 2.13
• Publications: 14 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-1382-A-C is Benign according to our data. Variant chrM-1382-A-C is described in ClinVar as Benign. ClinVar VariationId is 42214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 37

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.735A>C		non_coding_transcript_exon_variant	Exon 1 of 1
TRNV	unassigned_transcript_4786	c.-220A>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.735A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TV	ENST00000387342.1	n.-220A>C		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0031 AC: 192

Gnomad homoplasmic AF: 0.00066 AC: 37 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.00142 Hom.: 59

Mitomap

Disease(s): Longevity-/-T2D-susceptibility

Status: Reported

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 26, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.1120C>T in MTRNR1: This variant is not expected to have clinical significance because it has been found in the general population at a frequency of 0.5% (122/ 24187 human mitochondrial DNA sequences) with a haplogroup-specific frequency of 2.1% and 69.1% in two different Japanese clades (http://www.mitomap.org). Addit ionally, this variant is not significantly over represented in individuals with nonsyndromic hearing loss as it has been found in 43/1642 (2.6%) Chinese childre n (a proportion of whom have been exposed to aminoglycosides) as well as 9/449 ( 2.0%) Chinese controls (Lu 2010), suggesting that this variant is most likely no t involved in the observed hearing loss. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Other links and lift over

dbSNP: rs111033358; hg19: chrM-1384;