rs727504803

Positions:

• chrM-1375-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000389680.2(MT-RNR1):​n.728C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.00030 (AC: 18)
• Consequence: MT-RNR1 ENST00000389680.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -10.6

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 -4 ACMG points.

• BS2: High AC in GnomadMitoHomoplasmic at 14

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNR1	RNR1.1	n.728C>T		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.728C>T		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: 56432

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56432

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 05, 2013

Variant classified as Uncertain Significance - Favor Benign. The m.1375C>T varia nt in MT-RNR1 has not been reported in individuals with hearing loss, but it was identified in 18.0% (2/11) of New Guinean mitochondrial genomes (Ingman 2003) a nd 2.1% (1/48) of Chinese mitochondrial genomes (Kong 2006) in mitochondrial evo lutionary phylogeny studies (Human Mitochondrial Genome Database: http://www.mtd b.igp.uu.se; Human Mitochondrial Database: http://www.hmtdb.uniba.it:8080/hmdb). However, frequency of this variant in a larger cohort from these populations is needed to confidently rule out pathogenicity. In summary, the clinical signific ance of this variant cannot be determined; however, based on the current frequen cy data, we would lean towards a likely benign role. -

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: rs727504803; hg19: chrM-1377;