M-5802-T-C

Position:

• chrM-5802-T-C

Variant summary

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

The ENST00000387405.1(MT-TC):​n.25A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: MT-TC ENST00000387405.1 non_coding_transcript_exon
• 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

MT-TC (HGNC:7477): (mitochondrially encoded tRNA cysteine)

TRNC (HGNC:):

MT-TY (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/exons	MANE	Protein	UniProt
TRNC	TRNC.1	n.25A>G		non_coding_transcript_exon_variant	1/1
TRNY	TRNY.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TC	ENST00000387405.1	n.25A>G		non_coding_transcript_exon_variant	1/1
MT-TY	ENST00000387409.1			downstream_gene_variant

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

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

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

Jul 12, 2019

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C variant in MT-TC gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished).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;