M-5783-G-A

Position:

• chrM-5783-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3 BP6_Moderate BS2

The ENST00000387405.1(MT-TC):​n.44C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00070 (AC: 44)
• Consequence: MT-TC ENST00000387405.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 15
• Clinical Significance: Benign criteria provided, single submitter B:1 Myopathy-/-deafness-/-gout-/-tic-disorder
• Conservation: PhyloP100: 0.254

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 -5 ACMG points.

• PP3: Mitotip and hmtvar scores support pathogenic criterium.
• BP6: Variant M-5783-G-A is Benign according to our data. Variant chrM-5783-G-A is described in ClinVar as [Benign]. Clinvar id is 689987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 31

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNC	TRNC.1	n.44C>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.44C>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.

Mitomap GenBank AF: 0.00070 AC: 44

Gnomad homoplasmic AF: 0.00055 AC: 31 AN: 56430

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56430

Mitomap

Myopathy-/-deafness-/-gout-/-tic-disorder

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, 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.5783G>A variant in MT-TC gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	15
Hmtvar	Pathogenic	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603220110; hg19: chrM-5784;