rs118203890

chrM-15950-G-A

Variant summary

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

The ENST00000387460.2(MT-TT):n.63G>A 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: Absent
• Consequence: MT-TT ENST00000387460.2 non_coding_transcript_exon
• 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

MT-TT (HGNC:7499): (mitochondrially encoded tRNA threonine)

TRNT (HGNC:):

MT-TP (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/exons	MANE	UniProt
TRNT	TRNT.1	n.63G>A		non_coding_transcript_exon_variant	1/1
TRNP	TRNP.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TT	ENST00000387460.2	n.63G>A		non_coding_transcript_exon_variant	1/1
MT-TP	ENST00000387461.2			downstream_gene_variant

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

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

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

Jul 12, 2019

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A variant in MT-TT gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished).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

risk factor, no assertion criteria provided

literature only

OMIM

Apr 01, 1999

- -

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;