M-14701-C-T

Position:

• chrM-14701-C-T

Variant summary

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

The ENST00000387459.1(MT-TE):​n.42G>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: 𝑓 0.0 (AC: 0)
• Consequence: MT-TE ENST00000387459.1 non_coding_transcript_exon
• Scores: Mitotip Benign 7.6
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts P:1 U:2 Reversible-infantile-respiratory-chain-deficiency-(RIRCD)
• Conservation: PhyloP100: -4.73

Genes affected

MT-TE (HGNC:7479): (mitochondrially encoded tRNA glutamic acid)

TRNE (HGNC:):

MT-ND6 (HGNC:7462): (mitochondrially encoded NADH dehydrogenase 6) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy; Leigh disease; and spinal muscular atrophy with lower extremity predominante 2B. [provided by Alliance of Genome Resources, Apr 2022]

MT-CYB (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]

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
TRNE	TRNE.1	n.42G>A		non_coding_transcript_exon_variant	1/1
CYTB	CYTB.1			upstream_gene_variant			YP_003024038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TE	ENST00000387459.1	n.42G>A		non_coding_transcript_exon_variant	1/1
MT-ND6	ENST00000361681.2			upstream_gene_variant				ENSP00000354665	P1
MT-CYB	ENST00000361789.2			upstream_gene_variant				ENSP00000354554	P1

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: 56434

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56434

Mitomap

Reversible-infantile-respiratory-chain-deficiency-(RIRCD)

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial myopathy with reversible cytochrome C oxidase deficiency Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet

Dec 01, 2020

- -

See cases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Sep 24, 2019

This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2. -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Mar 20, 2018

This variant affects the MT-TE gene, which encodes the mitochondrial tRNA for glutamic acid, and has not been reported in the medical literature, is not listed in gene-specific variant databases, nor has it been previously identified in our laboratory. It is also absent from population databases such as MITOMAP. This variant disrupts a weakly conserved nucleotide, and several primate species, including the gorilla, gibbon, and rhesus monkey, have a thymine at this position, suggesting this variant is evolutionary tolerated. However, based on the available information, the clinical significance of the m.14701C>T variant cannot be determined with certainty. Pathogenic variants in MT-TE have been associated with mitochondrial disorders. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	7.6
Hmtvar	Benign	0.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1569484669; hg19: chrM-14702;