M-4317-A-G

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387365.1. 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-TI	ENST00000387365.1	TSL:6	n.55A>G		non_coding_transcript_exon	Exon 1 of 1
	MT-ND2	ENST00000361453.3	TSL:6	c.-153A>G		upstream_gene	N/A	ENSP00000355046.4
	MT-ND1	ENST00000361390.2	TSL:6	c.*55A>G		downstream_gene	N/A	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 v4.9

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;