rs267606889

Variant names:

• chrM-4681-T-C
• rs267606889
• unassigned_transcript_4793:c.212T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 1)
• Consequence: ND2 missense
• Scores: Apogee2 Pathogenic 0.73
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1 Leigh-Syndrome
• Conservation: PhyloP100: 7.63

Genes affected

ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNM (HGNC:7492): (mitochondrially encoded tRNA methionine)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-4681-T-C is Pathogenic according to our data. Variant chrM-4681-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 9721.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND2	unassigned_transcript_4793	c.212T>C	p.Leu71Pro	missense_variant	Exon 1 of 1
TRNM	unassigned_transcript_4792	c.*212T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	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: 1

Mitomap

Leigh-Syndrome

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Leigh syndrome due to mitochondrial complex I deficiency Pathogenic:1

Nov 01, 2006

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Leigh syndrome Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.73
Hmtvar	Pathogenic	0.89
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.000084	T
DEOGEN2	Benign	0.30	T
LIST_S2	Benign	0.58	T
MutationAssessor	Pathogenic	4.6	H
PROVEAN	Uncertain	-4.3	D
Sift4G	Pathogenic	0.0	D
GERP RS		4.3
Varity_R		0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs267606889; hg19: chrM-4682;