M-7468-C-T

Position:

• chrM-7468-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000387416.2(MT-TS1):​n.47G>A 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 0.00090 (AC: 58)
• Consequence: MT-TS1 ENST00000387416.2 non_coding_transcript_exon
• Scores: Mitotip Benign 0.42
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:2 B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.156

Genes affected

MT-TS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

TRNS1 (HGNC:):

MT-CO1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

MT-TD (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-7468-C-T is Benign according to our data. Variant chrM-7468-C-T is described in ClinVar as [Benign]. Clinvar id is 42224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 16

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNS1	TRNS1.1	n.47G>A		non_coding_transcript_exon_variant	1/1
COX1	COX1.1			downstream_gene_variant			YP_003024028.1
TRND	TRND.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TS1	ENST00000387416.2	n.47G>A		non_coding_transcript_exon_variant	1/1
MT-CO1	ENST00000361624.2			downstream_gene_variant				ENSP00000354499	P1
MT-TD	ENST00000387419.1			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: 0.00090 AC: 58

Gnomad homoplasmic AF: 0.00028 AC: 16 AN: 56432

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56432

Alfa AF: 0.000426 Hom.: 2

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Uncertain:2 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:2

Uncertain significance, no assertion criteria provided	clinical testing	Stanford Center for Inherited Cardiovascular Disease, Stanford University	Feb 07, 2013	Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. MTTS1 m.7468C>T With the information available at this time, it is not possible to determine whether this is a disease-causing mutation or a benign rare variant. The variant m.7468 C>T in the gene MTTS1 has not been reported in Mitomap (mitomap.org) as a mutation or as a benign polymorphism, and it has been seen very infrequently in the general population: 0 of 2704 individuals in mtDB (genpat.uu.se/mtDB), 0 of 3735 MitoWheel (http://mitowheel.org/mitowheel.html). It is located at the T-stem of the MT-tRNA Ser 1 and changes a G-T wobble base pair to an A:T Watson-Crick base pair, which may affect the secondary structure of the MT-tRNA Ser 1. This change occurs at a position that is conserved in 119 of 136 mammal species, but in the other mammal species an A:T Watson-Crick base pair is observed at this position. -
Uncertain significance, no assertion criteria provided	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2009	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 18, 2019

- -

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.7468C>T variant in MT-TS1 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	0.42
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: rs111033173; hg19: chrM-7469;