M-3350-T-C

Variant names:

• chrM-3350-T-C
• rs1603218915
• ENST00000361390.2:c.44T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361390.2(MT-ND1):​c.44T>C​(p.Ile15Thr) variant causes a missense change. 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. I15V) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.00030 (AC: 20)
• Consequence: MT-ND1 ENST00000361390.2 missense
• Scores: Apogee2 Benign 0.22
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 5.81
• Publications: 0 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: Benign. The variant received -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.2217416 < 0.5 .
• BP6: Variant M-3350-T-C is Benign according to our data. Variant chrM-3350-T-C is described in ClinVar as Benign. ClinVar VariationId is 692342.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 21

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

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-ND1	ENST00000361390.2	TSL:6	c.44T>C	p.Ile15Thr	missense	Exon 1 of 1	ENSP00000354687.2	P03886
	MT-TL1	ENST00000386347.1	TSL:6	n.*46T>C		downstream_gene	N/A
	MT-RNR2	ENST00000387347.2	TSL:6	n.*121T>C		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00030 AC: 20

Gnomad homoplasmic AF: 0.00037 AC: 21 AN: 56430

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56430

Alfa AF: 0.000445 Hom.: 2

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.22
Hmtvar	Benign	0.15
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.092	T
DEOGEN2	Benign	0.10	T
LIST_S2	Benign	0.48	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.8
PROVEAN	Uncertain	-3.0	D
Sift4G	Uncertain	0.020	D
GERP RS		3.6
Varity_R		0.59

Other links and lift over

dbSNP: rs1603218915; hg19: chrM-3351;