rs121434465

Variant names:

• chrM-4317-A-G
• rs121434465
• unassigned_transcript_4790:c.55A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000000000(TRNI):​c.55A>G​(p.Thr19Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00080 (AC: 48)
• Consequence: TRNI ENST00000000000 missense
• Scores: Mitotip Benign 1.9
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 FICP-/-poss.-Hypertension-/-DEAF-factor
• Conservation: PhyloP100: -0.746
• Publications: 3 publications found

Genes affected

TRNI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

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]

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]

TRNM (HGNC:7492): (mitochondrially encoded tRNA methionine)

TRNQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

TRNQ Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant M-4317-A-G is Benign according to our data. Variant chrM-4317-A-G is described in ClinVar as Benign. ClinVar VariationId is 9601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 28

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNI	unassigned_transcript_4790	c.55A>G	p.Thr19Ala	missense_variant	Exon 1 of 1
ND2	unassigned_transcript_4793	c.-153A>G		upstream_gene_variant
TRNM	unassigned_transcript_4792	c.-85A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.-153A>G		upstream_gene_variant		6		ENSP00000355046.4
MT-ND1	ENST00000361390.2	c.*55A>G		downstream_gene_variant		6		ENSP00000354687.2

Frequencies

Mitomap GenBank AF: 0.00080 AC: 48

Gnomad homoplasmic AF: 0.00050 AC: 28 AN: 56426

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56426

Alfa AF: 0.00103 Hom.: 19

Mitomap

Disease(s): FICP-/-poss.-Hypertension-/-DEAF-factor

Status: Reported

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiomyopathy, fatal infantile Pathogenic:1

May 09, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

MELAS syndrome Benign:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.4317A>G variant in MT-TI gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	1.9
Hmtvar	Pathogenic	0.50
PhyloP100		-0.75

Other links and lift over

dbSNP: rs121434465; hg19: chrM-4318;