M-5809-G-A

Position:

• chrM-5809-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000387405.1(MT-TC):​n.18C>T variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-TC ENST00000387405.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 15
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 Hearing-loss-patient
• Conservation: PhyloP100: 6.27

Genes affected

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

TRNC (HGNC:):

MT-TY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNC	TRNC.1	n.18C>T		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.18C>T		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.

Gnomad homoplasmic AF: 0.000053 AC: 3 AN: 56424

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56424

Mitomap

Hearing-loss-patient

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.5809G>A variant in MT-TC gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished).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: PP3, PP6, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	15
Hmtvar	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603220134; hg19: chrM-5810;