rs121434475

chrM-9997-T-AchrM-9997-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The ENST00000387429.1(MT-TG):n.7T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-TG ENST00000387429.1 non_coding_transcript_exon
• Scores: Mitotip Pathogenic 20
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1 Unspecified-patient-from-clinical-lab,MHCM
• Conservation: PhyloP100: 1.32

Genes affected

MT-TG (HGNC:7486): (mitochondrially encoded tRNA glycine)

TRNG (HGNC:):

MT-CO3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-9997-T-A is Pathogenic according to our data. Variant chrM-9997-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 690090.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNG	TRNG.1	n.7T>A		non_coding_transcript_exon_variant	1/1
COX3	COX3.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TG	ENST00000387429.1	n.7T>A		non_coding_transcript_exon_variant	1/1
MT-CO3	ENST00000362079.2			downstream_gene_variant				P1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap

Unspecified-patient-from-clinical-lab,MHCM

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely pathogenic, 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.9997T>A variant in MT-TG gene is interpreted to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PM5, PM7, PM9, PM10 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Pathogenic	20
Hmtvar	Benign	0.050

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs121434475; hg19: chrM-9998;