rs121434469

Positions:

• chrM-4290-T-C

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: 𝑓 0.0 (AC: 0)
• Consequence: TRNI synonymous
• Scores: Mitotip Uncertain 13
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1 Progressive-Encephalopathy-/-PEO+myopathy
• Conservation: PhyloP100: 3.97

Genes affected

TRNI (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNI	unassigned_transcript_4791	c.28T>C	p.Leu10Leu	synonymous_variant	1/1
ND1	unassigned_transcript_4790	c.*28T>C		downstream_gene_variant
TRNQ	unassigned_transcript_4792	c.*39A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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.

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56425

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56425

Mitomap

Progressive-Encephalopathy-/-PEO+myopathy

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Encephalopathy, familial progressive necrotizing Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2004

- -

MELAS syndrome 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.4290T>C variant in MT-TI gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished).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, BS4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	13
Hmtvar	Pathogenic	1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs121434469; hg19: chrM-4291;