rs28358573

Variant names:

• chrM-1442-G-A
• rs28358573
• unassigned_transcript_4785:n.795G>A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0060 (AC: 364)
• Consequence: RNR1 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.166

Genes affected

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)

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant M-1442-G-A is Benign according to our data. Variant chrM-1442-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 42221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: High frequency in mitomap database: 0.006
• BS2: High AC in GnomadMitoHomoplasmic at 1600

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.795G>A		non_coding_transcript_exon_variant	Exon 1 of 1
TRNV	unassigned_transcript_4786	c.-160G>A		upstream_gene_variant
RNR2	unassigned_transcript_4787	n.-229G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0060 AC: 364

Gnomad homoplasmic AF: 0.028 AC: 1600 AN: 56394

Gnomad heteroplasmic AF: 0.00012 AC: 7 AN: 56394

Alfa AF: 0.00255 Hom.: 89

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Apr 16, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.1442G>A in MTRNR1: This variant has been reported in 8% (10/120) of chromosom es from an African population sequenced by the 1000 Genome Project (dbSNP rs2835 8573). It has also been reported in broad populations at 1-4% frequency (LOVD da tabase http://www.lovd.nl/2.0; mtDB http://www.mtdb.igp.uu.se; HmtDB http://www. hmtdb.uniba.it:8080/hmdb) and belongs to the R7a'b haplotype group (http://www.f amilytreedna.com/mtDNA-Haplogroup-Mutations.aspx#). It has been identified in 3/ 1806 patients with hearing loss (0.2%) as well as in 4/675 controls (0.5%) (Li 2 004, Lu 2010). In summary, in the absence of any statistically significant assoc iation to hearing loss, the frequency of this variant suggests that it is likel y benign. -

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 19, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28358573; hg19: chrM-1444;