rs727504555

Positions:

• chrM-1027-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP5_Moderate BS2

The ENST00000389680.2(MT-RNR1):​n.380A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Mitomap GenBank: 𝑓 0.00030 (AC: 18)
• Consequence: MT-RNR1 ENST00000389680.2 non_coding_transcript_exon
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1 DEAF-associated
• Conservation: PhyloP100: 1.04

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]

RNR1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PP5: Variant M-1027-A-G is Pathogenic according to our data. Variant chrM-1027-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 178943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 14

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNR1	RNR1.1	n.380A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.380A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.00030 AC: 18

Gnomad homoplasmic AF: 0.00025 AC: 14 AN: 56428

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56428

Mitomap

DEAF-associated

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rare genetic deafness Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 08, 2013

The 1027A>G variant in MTRNR1 has been reported in five Chinese individuals with severe to profound hearing loss (four of whom were exposed to aminoglycosides), and the variant was absent from 449 ethnically matched controls (Shen 2011, Lu 2010). The variant segregated with disease in two maternal relatives (consistent with a mitochondrial inheritance pattern) of an additional Chinese proband with severe hearing loss who was not exposed to aminoglycosides (Shen 2011). This v ariant has not been reported in the Human Mitochondrial Genome Database, which i ncludes a total of 2704 mitochondrial genomes of which 52 are from Chinese indiv iduals (www.mtdb.igp.uu.se). In summary, this variant is likely pathogenic based on the observation of the variant in individuals with hearing loss, though addi tional studies are required to fully establish its clinical significance. -

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: rs727504555; hg19: chrM-1029;