M-1040-T-C

Variant names:

• chrM-1040-T-C
• rs727503163
• ENST00000389680.2:n.393T>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.393T>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 0.0032 (AC: 194)
• 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: -14.8
• 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-1040-T-C is Benign according to our data. Variant chrM-1040-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 163983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 305

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-RNR1	ENST00000389680.2	TSL:6	n.393T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

Mitomap GenBank AF: 0.0032 AC: 194

Gnomad homoplasmic AF: 0.0054 AC: 305 AN: 56423

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56423

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 25, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.1040T>C in MTRNR1: This variant is not expected to have clinical significance because it has been reported at high frequency in several haplogroups, including 41.1% (44/107) of L2c, 100% (6/6) of R22, and 2% (3/151) of haplogroup C (MITO MAP; https://www.mitomap.org/MITOMAP).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-15

Other links and lift over

dbSNP: rs727503163; hg19: chrM-1042;