M-3336-T-G

Variant names:

• chrM-3336-T-G
• rs28416101
• ENST00000361390.2:c.30T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000361390.2(MT-ND1):​c.30T>G​(p.Ile10Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I10T) has been classified as Benign.

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-ND1 ENST00000361390.2 missense
• Scores: Apogee2 Benign 0.26
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -5.56
• Publications: 12 publications found

Genes affected

MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

TRNL1 (HGNC:7490): (mitochondrially encoded tRNA leucine 1 (UUA/G)) Implicated in cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR2 (HGNC:7471): (mitochondrially encoded 16S RNA) Enables G protein-coupled receptor binding activity; protein self-association; and receptor antagonist activity. Involved in several processes, including leukocyte chemotaxis; negative regulation of cell death; and negative regulation of neuroinflammatory response. Located in several cellular components, including mitochondrion; perinuclear region of cytoplasm; and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• BP4: Apogee2 supports a benign effect, 0.25830206 < 0.5 .

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361390.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND1	ENST00000361390.2	TSL:6	c.30T>G	p.Ile10Met	missense	Exon 1 of 1	ENSP00000354687.2
	MT-TL1	ENST00000386347.1	TSL:6	n.*32T>G		downstream_gene	N/A
	MT-RNR2	ENST00000387347.2	TSL:6	n.*107T>G		downstream_gene	N/A

Frequencies

Mitomap GenBank The variant is not present, suggesting it is rare .

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.26
Hmtvar	Pathogenic	0.58
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.53	T
DEOGEN2	Benign	0.043	T
LIST_S2	Benign	0.80	T
MutationAssessor	Benign	1.2	L
PhyloP100		-5.6
PROVEAN	Benign	-1.9	N
Sift4G	Uncertain	0.049	D
GERP RS		-4.0
Varity_R		0.63

Other links and lift over

dbSNP: rs28416101; hg19: chrM-3337;