M-4305-A-G

Position:

• chrM-4305-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000387365.1(MT-TI):​n.43A>G variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TI ENST00000387365.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 12
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 8.84

Genes affected

MT-TI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

TRNI (HGNC:):

MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

MT-TQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Mitotip and hmtvar scores support benign criterium.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNI	TRNI.1	n.43A>G		non_coding_transcript_exon_variant	1/1
TRNQ	TRNQ.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TI	ENST00000387365.1	n.43A>G		non_coding_transcript_exon_variant	1/1
MT-ND1	ENST00000361390.2			downstream_gene_variant				ENSP00000354687	P1
MT-TQ	ENST00000387372.1			downstream_gene_variant

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

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

May 24, 2018

The MT-TI m.4305A>G variant affects the mitochondrially-encoded tRNAs for isoleucine. This variant has not been reported in the medical literature in association with disease and is absent from the MITOMAP database. Thus, based on the available information, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	12
Hmtvar	Benign	0.050

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1569483932; hg19: chrM-4306;