M-14693-A-G

Position:

• chrM-14693-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The ENST00000387459.1(MT-TE):​n.50T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0058 (AC: 352)
• Consequence: MT-TE ENST00000387459.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 11
• Clinical Significance: Benign criteria provided, single submitter B:1 MELAS-/-LHON-/-DEAF-/-hypertension-helper
• Conservation: PhyloP100: 0.777

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-14693-A-G is Benign according to our data. Variant chrM-14693-A-G is described in ClinVar as [Benign]. Clinvar id is 690204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: High frequency in mitomap database: 0.0058
• BS2: High AC in GnomadMitoHomoplasmic at 109

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNE	TRNE.1	n.50T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TE	ENST00000387459.1	n.50T>C		non_coding_transcript_exon_variant	1/1
MT-ND6	ENST00000361681.2			upstream_gene_variant				ENSP00000354665	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: 0.0058 AC: 352

Gnomad homoplasmic AF: 0.0019 AC: 109 AN: 56426

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56426

Alfa AF: 0.000445 Hom.: 2

Mitomap

MELAS-/-LHON-/-DEAF-/-hypertension-helper

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, 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.14693A>G variant in MT-TE gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	11
Hmtvar	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs386829226; hg19: chrM-14694;