rs1556422538

Variant names:

• chrM-1473-C-T
• rs1556422538
• ENST00000389680.2:n.826C>T

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.826C>T 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: 595)
• 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: 1.37
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant M-1473-C-T is Benign according to our data. Variant chrM-1473-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 505288.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 61

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.826C>T		non_coding_transcript_exon_variant	Exon 1 of 1
TRNV	unassigned_transcript_4786	c.-129C>T		upstream_gene_variant
RNR2	unassigned_transcript_4787	n.-198C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.826C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TV	ENST00000387342.1	n.-129C>T		upstream_gene_variant		6
MT-RNR2	ENST00000387347.2	n.-198C>T		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0097 AC: 595

Gnomad homoplasmic AF: 0.0011 AC: 61 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 24, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.1473C>T in MTRNR1: This variant is not expected to have clinical significance because it has not been reported in individuals with hearing loss, and it has be en identified in 0.3% (4/1320) of human mitochondrial DNA sequences of the haplo group B4a (http://www.mitomap.org). Furthermore, 10 species have a thymine (T) a t this position, including 6 mammals (squirrel, Egyptian jerboa, prarie vole, Ch inese hamster, golden hamster, mouse). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Other links and lift over

dbSNP: rs1556422538; hg19: chrM-1475;