M-951-G-A

Variant names:

• chrM-951-G-A
• rs200887992
• ENST00000389680.2:n.304G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000000000(RNR1):​n.304G>A 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 0.0072 (AC: 440)
• Consequence: RNR1 ENST00000000000 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.114
• Publications: 7 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: Benign. The variant received -10 ACMG points.

• BP6: Variant M-951-G-A is Benign according to our data. Variant chrM-951-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 42231.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: High frequency in mitomap database: 0.0072000003
• BS2: High AC in GnomadMitoHomoplasmic at 426

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.304G>A		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.304G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

Mitomap GenBank AF: 0.0072 AC: 440

Gnomad homoplasmic AF: 0.0075 AC: 426 AN: 56426

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56426

Alfa AF: 0.00669 Hom.: 305

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 28, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.951G>A in MTRNR1: This variant is reported with low frequency, 0.1-4%, in broa d populations (LOVD database 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 H2a mitochond rial haplogroup (Brandstatter 2006). It has been identified in patients with hea ring loss (0.4 ? 1.6%) as well as in controls (0.4 - 1%) without a statistically significant difference (Konings 2008, Li_2004, Lu 2010, Rydzanicz 2010). In sum mary, in the absence of any statistically significant association to hearing los s, the frequency of this variant suggests that it is likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11

Other links and lift over

dbSNP: rs200887992; hg19: chrM-953;