ENST00000361390.2:c.51G>A

Variant names:

• chrM-3357-G-A
• rs1556422714
• ENST00000361390.2:c.51G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP7 BS2

The ENST00000361390.2(MT-ND1):​c.51G>A​(p.Met17Met) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.0012 (AC: 76)
• Consequence: MT-ND1 ENST00000361390.2 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -0.477
• 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: Likely_benign. The variant received -5 ACMG points.

• BP7: Synonymous conserved (PhyloP=-0.477 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 25

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND1	unassigned_transcript_4789	c.51G>A	p.Met17Met	synonymous_variant	Exon 1 of 1
TRNL1	unassigned_transcript_4788	c.*53G>A		downstream_gene_variant
RNR2	unassigned_transcript_4787	n.*128G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND1	ENST00000361390.2	c.51G>A	p.Met17Met	synonymous_variant	Exon 1 of 1	6		ENSP00000354687.2
MT-TL1	ENST00000386347.1	n.*53G>A		downstream_gene_variant		6
MT-RNR2	ENST00000387347.2	n.*128G>A		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0012 AC: 76

Gnomad homoplasmic AF: 0.00044 AC: 25 AN: 56431

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56431

Alfa AF: 0.000890 Hom.: 4

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.50	T
DEOGEN2	Benign	0.012	T
LIST_S2	Benign	0.75	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-0.48
PROVEAN	Benign	0.96	N
GERP RS		1.5
Varity_R		0.36
Mutation Taster		=29/71	disease causing

Other links and lift over

dbSNP: rs1556422714; hg19: chrM-3358;