M-7472-A-T

Position:

• chrM-7472-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

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

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 14)
• Consequence: TRNS1 missense
• Scores: Mitotip Benign 2.4
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.563

Genes affected

TRNS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

TRND (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

COX1 (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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant M-7472-A-T is Benign according to our data. Variant chrM-7472-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 505297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNS1	unassigned_transcript_4800	c.43T>A	p.Trp15Arg	missense_variant	1/1
TRND	unassigned_transcript_4801	c.-46A>T		upstream_gene_variant
COX1	unassigned_transcript_4799	c.*27A>T		downstream_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 GenBank AF: 0.00020 AC: 14

Gnomad homoplasmic AF: 0.00012 AC: 7 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 24, 2016

m.7472A>T in MTTS1: This variant is not expected to have clinical significance b ecause it has been identified in all individuals from haplotype H7g (5/5) as rep orted in MitoMap (http://www.mitomap.org). In addition, this variant was reporte d in 1 individual with a suspected mitochondrial disease, but was also detected in the individual's asymptomatic mother. Both the individual and their mother w ere homoplasmic for the variant and belonged to mtDNA haplogroup H (Tang 2013). Furthermore, the nucleotide at position m.7472 is not conserved with >10 specie s, including 3 mammals (Bactrian camel, cat, Cape golden mole) having a T at thi s position. Collectively, this data supports that the variant is likely benign. -

MELAS syndrome 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.7472A>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, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.4
Hmtvar	Benign	0.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556423293; hg19: chrM-7473;