rs118203890

Variant names:

• chrM-15950-G-A
• rs118203890
• unassigned_transcript_4819:c.63G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNT synonymous
• Scores: Mitotip Uncertain 13
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1 LHON-/-LHON-MS-/-dopaminergic-nerve-cell-death-(PD)-/-tic-disorder
• Conservation: PhyloP100: 1.53

Genes affected

TRNT (HGNC:7499): (mitochondrially encoded tRNA threonine)

CYTB (HGNC:7427): (mitochondrially encoded cytochrome b) Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including electron transport coupled proton transport; response to cobalamin; and response to glucagon. Located in mitochondrion. Implicated in ovarian carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNP (HGNC:7494): (mitochondrially encoded tRNA proline)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNT	unassigned_transcript_4819	c.63G>A	p.Arg21Arg	synonymous_variant	Exon 1 of 1
CYTB	unassigned_transcript_4818	c.*63G>A		downstream_gene_variant
TRNP	unassigned_transcript_4820	c.*6C>T		downstream_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.

Gnomad homoplasmic AF: 0.000053 AC: 3 AN: 56430

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56430

Mitomap

LHON-/-LHON-MS-/-dopaminergic-nerve-cell-death-(PD)-/-tic-disorder

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Uncertain:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.15950G>A variant in MT-TT gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PP3, BP6 -

Parkinson disease, mitochondrial Other:1

Apr 01, 1999

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	13
Hmtvar	Benign	0.10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs118203890; hg19: chrM-15951;