chrM-7512-T-C

Position:

• chrM-7512-T-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2 PP5_Very_Strong

Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNS1 synonymous
• Scores: Mitotip Uncertain 14
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:5 O:1 PEM-/-MERME-/-MELAS
• Conservation: PhyloP100: 2.12

Genes affected

TRNS1 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-7512-T-C is Pathogenic according to our data. Variant chrM-7512-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 9562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNS1	unassigned_transcript_4801	c.3A>G	p.Glu1Glu	synonymous_variant	1/1
TRND	unassigned_transcript_4802	c.-6T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap

PEM-/-MERME-/-MELAS

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:5 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

MERRF/MELAS overlap syndrome Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Nov 01, 1998	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	MGZ Medical Genetics Center	Jun 30, 2022	VAF 50% heteroplasmy in blood, several affected family members -

MELAS syndrome Pathogenic:1 Other:1

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.7512T>C variant in MT-TS1 gene is interpreted to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PS3, PS5, PP3 -
not provided, no classification provided	literature only	GeneReviews	-	- -

Mitochondrial complex IV deficiency, nuclear type 1 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Mitochondrial cytochrome c oxidase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	14
Hmtvar	Pathogenic	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199474817; hg19: chrM-7513;