M-5553-T-G

Variant names:

• chrM-5553-T-G
• rs878853053
• unassigned_transcript_4794:c.42T>G

Variant summary

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

The ENST00000000000(TRNW):​c.42T>G​(p.Pro14Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 6)
• Consequence: TRNW ENST00000000000 synonymous
• Scores: Mitotip Uncertain 11
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

Genes affected

TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

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]

TRNN (HGNC:7493): (mitochondrially encoded tRNA asparagine)

TRNA (HGNC:7475): (mitochondrially encoded tRNA alanine)

TRNC (HGNC:7477): (mitochondrially encoded tRNA cysteine)

TRNC 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=1.49 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 13

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNW	unassigned_transcript_4794	c.42T>G	p.Pro14Pro	synonymous_variant	Exon 1 of 1
ND2	unassigned_transcript_4793	c.*42T>G		downstream_gene_variant
TRNN	unassigned_transcript_4796	c.*104A>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.*42T>G		downstream_gene_variant		6		ENSP00000355046.4

Frequencies

Mitomap GenBank AF: 0.00010 AC: 6

Gnomad homoplasmic AF: 0.00023 AC: 13 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Benign:1

Jul 12, 2019

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.5553T>G variant in MT-TW gene is interpreted to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BP6 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	11
Hmtvar	Benign	0.0
PhyloP100		1.5

Other links and lift over

dbSNP: rs878853053; hg19: chrM-5554;