M-721-T-C

Variant names:

• chrM-721-T-C
• rs1556422479
• ENST00000389680.2:n.74T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000000000(RNR1):​n.74T>C variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0023 (AC: 139)
• Consequence: RNR1 ENST00000000000 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 Possibly-LVNC-associated
• Conservation: PhyloP100: 4.71
• 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]

TRNF (HGNC:7481): (mitochondrially encoded tRNA phenylalanine)

TRNF Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant M-721-T-C is Benign according to our data. Variant chrM-721-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 994690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 96

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.74T>C		non_coding_transcript_exon_variant	Exon 1 of 1
TRNF	unassigned_transcript_4784	c.*74T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.74T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TF	ENST00000387314.1	n.*74T>C		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0023 AC: 139

Gnomad homoplasmic AF: 0.0017 AC: 96 AN: 56424

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56424

Mitomap

Disease(s): Possibly-LVNC-associated

Status: Reported

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Aug 17, 2020

Athena Diagnostics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7
Mutation Taster		=59/41	polymorphism

Other links and lift over

dbSNP: rs1556422479; hg19: chrM-723;