rs386828884

Variant names:

• chrM-1508-C-T
• rs386828884
• ENST00000389680.2:n.861C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000389680.2(MT-RNR1):​n.861C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.00050 (AC: 28)
• 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: -6.34
• 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]

TRNV (HGNC:7500): (mitochondrially encoded tRNA valine)

MT-RNR2 (HGNC:7471): (mitochondrially encoded 16S RNA) Enables G protein-coupled receptor binding activity; protein self-association; and receptor antagonist activity. Involved in several processes, including leukocyte chemotaxis; negative regulation of cell death; and negative regulation of neuroinflammatory response. Located in several cellular components, including mitochondrion; perinuclear region of cytoplasm; and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomadMitoHomoplasmic at 19

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.861C>T		non_coding_transcript_exon_variant	Exon 1 of 1
TRNV	unassigned_transcript_4786	c.-94C>T		upstream_gene_variant
RNR2	unassigned_transcript_4787	n.-163C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.861C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TV	ENST00000387342.1	n.-94C>T		upstream_gene_variant		6
MT-RNR2	ENST00000387347.2	n.-163C>T		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00050 AC: 28

Gnomad homoplasmic AF: 0.00034 AC: 19 AN: 56431

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56431

Alfa AF: 0.000256 Hom.: 3

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 04, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1508C>T in MT-RNR1: This variant is not expected to have clinical significance b ecause it has been identified in several human phylogeny studies with haplogroup -specific frequencies ranging from 0.3% to 7.5% (http://www.hmtdb.uniba.it:8080/ hmdb/; http://www.mitomap.org; http://www.mtdb.igp.uu.se). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-6.3

Other links and lift over

dbSNP: rs386828884; hg19: chrM-1510;