M-5784-C-CT

Variant names:

• chrM-5784-C-CT
• rs1603220115
• unassigned_transcript_4797:c.42dupA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

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

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 2)
• Consequence: TRNC frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.390

Genes affected

TRNC (HGNC:7477): (mitochondrially encoded tRNA cysteine)

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]

TRNN (HGNC:7493): (mitochondrially encoded tRNA asparagine)

TRNA (HGNC:7475): (mitochondrially encoded tRNA alanine)

TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

TRNY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP6: Variant M-5784-C-CT is Benign according to our data. Variant chrM-5784-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 689990.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNC	unassigned_transcript_4797	c.42dupA	p.Ala15fs	frameshift_variant	Exon 1 of 1
COX1	unassigned_transcript_4799	c.-120_-119insT		upstream_gene_variant
TRNN	unassigned_transcript_4796	c.-56dupA		upstream_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: 0.0 AC: 2

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Benign:1

Jul 12, 2019

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.5786dupT variant in MT-TC gene is interpreted to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS4, BP6 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603220115; hg19: chrM-5785;