M-5663-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

Variant has been reported in ClinVar as Benign (★).

Frequency

Mitomap GenBank:
𝑓 0.00040 ( AC: 23 )

Consequence

TRNN
missense

Scores

Mitotip
Benign
0.53

Clinical Significance

Benign criteria provided, single submitter B:1
No linked disesase in Mitomap

Conservation

PhyloP100: 0.379
Variant links:
Genes affected
TRNN (HGNC:7493): (mitochondrially encoded tRNA asparagine)
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]
TRNA (HGNC:7475): (mitochondrially encoded tRNA alanine)
ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]
TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)
TRNC (HGNC:7477): (mitochondrially encoded tRNA cysteine)
TRNY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6
Variant M-5663-C-T is Benign according to our data. Variant chrM-5663-C-T is described in ClinVar as [Benign]. Clinvar id is 689969.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomadMitoHomoplasmic at 52

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRNNunassigned_transcript_4796 c.67G>A p.Gly23Ser missense_variant Exon 1 of 1
COX1unassigned_transcript_4799 c.-241C>T upstream_gene_variant
TRNAunassigned_transcript_4795 c.-8G>A 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:
0.00040
AC:
23
Gnomad homoplasmic
AF:
0.00092
AC:
52
AN:
56433
Gnomad heteroplasmic
AF:
0.0
AC:
0
AN:
56433

Mitomap

No disease associated.

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

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.5663C>T variant in MT-TN 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
0.53
Hmtvar
Benign
0.10

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1553139251; hg19: chrM-5664; API