rs878853115

Variant names:

• chrM-5302-T-C
• rs878853115
• ENST00000361453.3:c.833T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000361453.3(MT-ND2):​c.833T>C​(p.Ile278Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I278V) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.00090 (AC: 52)
• Consequence: MT-ND2 ENST00000361453.3 missense
• Scores: Apogee2 Benign 0.048
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.257
• Publications: 8 publications found

Genes affected

MT-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]

TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

TRNW Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.047591355 < 0.5 .
• BP6: Variant M-5302-T-C is Benign according to our data. Variant chrM-5302-T-C is described in ClinVar as Benign. ClinVar VariationId is 235811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 52

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361453.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND2	ENST00000361453.3	TSL:6	c.833T>C	p.Ile278Thr	missense	Exon 1 of 1	ENSP00000355046.4	P03891
	MT-TW	ENST00000387382.1	TSL:6	n.-210T>C		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00090 AC: 52

Gnomad homoplasmic AF: 0.00092 AC: 52 AN: 56415

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56415

Alfa AF: 0.00156 Hom.: 6

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.048
Hmtvar	Benign	0.090
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.56	T
DEOGEN2	Benign	0.065	T
LIST_S2	Benign	0.59	T
MutationAssessor	Benign	0.39	N
PhyloP100		0.26
PROVEAN	Uncertain	-2.5	D
Sift4G	Benign	0.43	T
GERP RS		3.0
Varity_R		0.11
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs878853115; hg19: chrM-5303;