M-5774-T-C

Position:

• chrM-5774-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000387405.1(MT-TC):​n.53A>G 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 0.0011 (AC: 66)
• Consequence: MT-TC ENST00000387405.1 non_coding_transcript_exon
• Scores: Mitotip Benign 1.2
• Clinical Significance: Benign criteria provided, single submitter B:1 Reported-in-tic-disorder-patient
• Conservation: PhyloP100: -4.29

Genes affected

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

TRNC (HGNC:):

MT-TN (HGNC:7493): (mitochondrially encoded tRNA asparagine)

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-5774-T-C is Benign according to our data. Variant chrM-5774-T-C is described in ClinVar as [Benign]. Clinvar id is 689983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 27

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNC	TRNC.1	n.53A>G		non_coding_transcript_exon_variant	1/1
TRNN	TRNN.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TC	ENST00000387405.1	n.53A>G		non_coding_transcript_exon_variant	1/1
MT-TN	ENST00000387400.1			upstream_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: 0.0011 AC: 66

Gnomad homoplasmic AF: 0.00048 AC: 27 AN: 56420

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56420

Mitomap

Reported-in-tic-disorder-patient

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.5774T>C variant in MT-TC gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	1.2
Hmtvar	Benign	0.10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603220102; hg19: chrM-5775;