M-3340-C-T

Variant names:

• chrM-3340-C-T
• rs1603218910
• ENST00000361390.2:c.34C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM2 BP4 BP6_Very_Strong

The ENST00000361390.2(MT-ND1):​c.34C>T​(p.Pro12Ser) 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 Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: MT-ND1 ENST00000361390.2 missense
• Scores: Apogee2 Benign 0.31
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 Encephaloneuromyopathy
• Conservation: PhyloP100: 1.31
• 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.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.30885056 < 0.5 .
• BP6: Variant M-3340-C-T is Benign according to our data. Variant chrM-3340-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 692339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.34C>T	p.Pro12Ser	missense	Exon 1 of 1	ENSP00000354687.2	P03886
	MT-TL1	ENST00000386347.1	TSL:6	n.*36C>T		downstream_gene	N/A
	MT-RNR2	ENST00000387347.2	TSL:6	n.*111C>T		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 3

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Mitomap

Disease(s): Encephaloneuromyopathy

Status: Reported

ClinVar

ClinVar submissions

Significance: Likely 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	0.31
Hmtvar	Benign	0.23
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.35	T
DEOGEN2	Benign	0.12	T
LIST_S2	Benign	0.76	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.3
PROVEAN	Pathogenic	-6.1	D
Sift4G	Uncertain	0.043	D
GERP RS		2.5
Varity_R		0.53
Mutation Taster		=86/14	polymorphism

Other links and lift over

dbSNP: rs1603218910; hg19: chrM-3341;