rs879192165

Positions:

• chrM-14692-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP5_Moderate BP4

The ENST00000387459.1(MT-TE):​n.51T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Mitomap GenBank: 𝑓 0.00040 (AC: 25)
• Consequence: MT-TE ENST00000387459.1 non_coding_transcript_exon
• Scores: Mitotip Benign 2.0
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 LHON-helper-/-Maternally-inherited-diabetes-&-deafness-/tic-disorder
• Conservation: PhyloP100: 1.86

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 Uncertain_significance. Variant got 1 ACMG points.

• PP5: Variant M-14692-A-G is Pathogenic according to our data. Variant chrM-14692-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 267298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Mitotip and hmtvar scores support benign criterium.. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNE	TRNE.1	n.51T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TE	ENST00000387459.1	n.51T>C		non_coding_transcript_exon_variant	1/1
MT-ND6	ENST00000361681.2			upstream_gene_variant				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: 0.00040 AC: 25

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56434

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56434

Mitomap

LHON-helper-/-Maternally-inherited-diabetes-&-deafness-/tic-disorder

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial disease Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Diabetes-deafness syndrome maternally transmitted Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 25, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.0
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: rs879192165; hg19: chrM-14693;