chrM-593-T-C

Position:

• chrM-593-T-C

Variant summary

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

The ENST00000387314.1(MT-TF):​n.17T>C 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 0.0048 (AC: 294)
• Consequence: MT-TF ENST00000387314.1 non_coding_transcript_exon
• Scores: Mitotip Benign 1.3
• Clinical Significance: Benign criteria provided, single submitter B:1 Nonsyndromic-hearing-loss-/-LHON
• Conservation: PhyloP100: -3.61

Genes affected

MT-TF (HGNC:7481): (mitochondrially encoded tRNA phenylalanine)

TRNF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-593-T-C is Benign according to our data. Variant chrM-593-T-C is described in ClinVar as [Benign]. Clinvar id is 689809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 140

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNF	TRNF.1	n.17T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TF	ENST00000387314.1	n.17T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0048 AC: 294

Gnomad homoplasmic AF: 0.0025 AC: 140 AN: 56418

Gnomad heteroplasmic AF: 0.00025 AC: 14 AN: 56418

Mitomap

Nonsyndromic-hearing-loss-/-LHON

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.593T>C variant in MT-TF gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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, BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	1.3
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: rs879123694; hg19: chrM-595;