chrM-4218-T-C

Variant names:

• chrM-4218-T-C
• rs878853061
• unassigned_transcript_4789:c.912T>C

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 0.0050 (AC: 306)
• Consequence: ND1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -6.11

Genes affected

ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

TRNI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

TRNM (HGNC:7492): (mitochondrially encoded tRNA methionine)

TRNQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant M-4218-T-C is Benign according to our data. Variant chrM-4218-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 235539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND1	unassigned_transcript_4789	c.912T>C	p.Tyr304Tyr	synonymous_variant	Exon 1 of 1
TRNI	unassigned_transcript_4790	c.-45T>C		upstream_gene_variant
TRNM	unassigned_transcript_4792	c.-184T>C		upstream_gene_variant
TRNQ	unassigned_transcript_4791	c.*111A>G		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: 0.0050 AC: 306

Gnomad homoplasmic AF: 0.014 AC: 787 AN: 56422

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56422

Alfa AF: 0.00179 Hom.: 8

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 18, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs878853061; hg19: chrM-4219;