rs727503163

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.393T>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.393T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

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 v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-15

Other links and lift over

dbSNP: rs727503163; hg19: chrM-1042;