M-12403-C-T

Variant names:

• chrM-12403-C-T
• rs879096684
• unassigned_transcript_4815:c.67C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0040 (AC: 247)
• Consequence: ND5 missense
• Scores: Apogee2 Benign 0.016
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -5.78

Genes affected

ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) 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; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNH (HGNC:7487): (mitochondrially encoded tRNA histidine)

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-12403-C-T is Benign according to our data. Variant chrM-12403-C-T is described in ClinVar as [Benign]. Clinvar id is 693435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 61

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND5	unassigned_transcript_4815	c.67C>T	p.Leu23Phe	missense_variant	Exon 1 of 1
TRNL2	unassigned_transcript_4814	c.*67C>T		downstream_gene_variant
TRNH	unassigned_transcript_4812	c.*197C>T		downstream_gene_variant
TRNS2	unassigned_transcript_4813	c.*138C>T		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: 0.0040 AC: 247

Gnomad homoplasmic AF: 0.0011 AC: 61 AN: 56434

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56434

Alfa AF: 0.00213 Hom.: 27

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Oct 17, 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.12403C>T (YP_003024036.1:p.Leu23Phe) variant in MTND5 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.016
Hmtvar	Benign	0.35
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.50	T
DEOGEN2	Benign	0.021	T
LIST_S2	Benign	0.49	T
MutationAssessor	Benign	1.9	L
PROVEAN	Benign	-0.92	N
Sift4G	Benign	0.21	T
GERP RS		-8.5
Varity_R		0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs879096684; hg19: chrM-12404;