ENST00000389680.2:n.333T>C

Variant names:

• chrM-980-T-C
• rs397515731
• ENST00000389680.2:n.333T>C

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.333T>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 0.0097 (AC: 590)
• 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: -8.54
• Publications: 1 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-980-T-C is Benign according to our data. Variant chrM-980-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 42237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: High frequency in mitomap database: 0.0097
• BS2: High AC in GnomadMitoHomoplasmic at 226

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.333T>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.333T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

Mitomap GenBank AF: 0.0097 AC: 590

Gnomad homoplasmic AF: 0.0040 AC: 226 AN: 56421

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56421

Alfa AF: 0.00358 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

Jan 09, 2018

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.980T>C in MTRNR1: This variant has been observed in 2/1642 patients with heari ng loss and was absent from 449 controls (Lu 2010). However, this variant is als o reported with similar frequencies in broad populations (LOVD database http://w ww.lovd.nl/2.0; mtDB http://www.mtdb.igp.uu.se; HmtDB http://www.hmtdb.uniba.it: 8080/hmdb). Moreover, this region of mitochondrial DNA is not conserved. Of note , mouse, Xenopus, Drosophila and E. coli have a C at this position (Conrad 2008) . In summary, there is no data to support a disease-associated role and the popu lation frequency suggests that this variant is likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-8.5
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs397515731; hg19: chrM-982;