rs1556422495

Positions:

• chrM-953-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000389680.2(MT-RNR1):​n.306T>C 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 0.00020 (AC: 11)
• 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: -5.93

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.

• BP6: Variant M-953-T-C is Benign according to our data. Variant chrM-953-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 517299.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNR1	RNR1.1	n.306T>C		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.306T>C		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: 0.00020 AC: 11

Gnomad homoplasmic AF: 0.000053 AC: 3 AN: 56419

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56419

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 02, 2017

m.953T>C in MTRNR1: This variant is not expected to have clinical significance b ecause it has been identified in 2.4% (3/125) of human mitochondrial DNA sequenc es of the haplogroup N1a, which is of South Asian origin (http://www.mitomap.org ). Furthermore, the thymine (T) nucleotide at position m.953 is not conserved in mammals or evolutionarily distant species, and 11 species carry a cytosine (C) at this position, supporting that this change may be tolerated. Though this vari ant has been identified in several individuals with hearing loss (Lu 2010), the high frequency of this variant in haplogroup N1a indicates it is likely benign. -

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: rs1556422495; hg19: chrM-955;