rs111033324

Variant names:

• chrM-7498-G-A
• rs111033324
• unassigned_transcript_4800:c.17C>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 Benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0017 (AC: 104)
• Consequence: TRNS1 missense
• Scores: Mitotip Benign 2.8
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.648

Genes affected

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

COX2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

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-7498-G-A is Benign according to our data. Variant chrM-7498-G-A is described in ClinVar as [Benign]. Clinvar id is 42230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 236

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNS1	unassigned_transcript_4800	c.17C>T	p.Ala6Val	missense_variant	Exon 1 of 1
COX2	unassigned_transcript_4802	c.-88G>A		upstream_gene_variant
TRND	unassigned_transcript_4801	c.-20G>A		upstream_gene_variant
COX1	unassigned_transcript_4799	c.*53G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	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: 0.0017 AC: 104

Gnomad homoplasmic AF: 0.0042 AC: 236 AN: 56420

Gnomad heteroplasmic AF: 0.00018 AC: 10 AN: 56420

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 13, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.7498G>A in MTTS1: This variant is not expected to have clinical significance b ecause it has been found at high frequency in the general population, including 8.8% (40/456) of the African L1c haplogroup and 34.6% (9/26) of the Asian C5b ha plogroup (http://www.mitomap.org). -

MELAS syndrome Benign:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.7498G>A 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	2.8
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: rs111033324; hg19: chrM-7499;