M-5802-T-C

Variant names:

• chrM-5802-T-C
• rs1603220128
• unassigned_transcript_4797:c.25A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS2

Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: TRNC missense
• Scores: Mitotip Uncertain 13
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 DEAF1555-increased-penetrance-/-obesity-risk
• Conservation: PhyloP100: 2.24

Genes affected

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

COX1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

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

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

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

TRNY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BS2: High AC in GnomadMitoHomoplasmic at 4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNC	unassigned_transcript_4797	c.25A>G	p.Asn9Asp	missense_variant	Exon 1 of 1
COX1	unassigned_transcript_4799	c.-102T>C		upstream_gene_variant
TRNN	unassigned_transcript_4796	c.-73A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0 AC: 3

Gnomad homoplasmic AF: 0.000071 AC: 4 AN: 56434

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56434

Mitomap

DEAF1555-increased-penetrance-/-obesity-risk

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Uncertain:1

Jul 12, 2019

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.5802T>C variant in MT-TC gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS2, BP5, PP3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	13
Hmtvar	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1603220128; hg19: chrM-5803;