M-12389-C-T

Variant names:

• chrM-12389-C-T
• rs1603223710
• unassigned_transcript_4815:c.53C>T

Variant summary

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

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

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 6)
• Consequence: ND5 missense
• Scores: Apogee2 Benign 0.26
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 4.56

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND5	unassigned_transcript_4815	c.53C>T	p.Pro18Leu	missense_variant	Exon 1 of 1
TRNL2	unassigned_transcript_4814	c.*53C>T		downstream_gene_variant
TRNH	unassigned_transcript_4812	c.*183C>T		downstream_gene_variant
TRNS2	unassigned_transcript_4813	c.*124C>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: 0.00010 AC: 6

Gnomad homoplasmic AF: 0.000035 AC: 2 AN: 56432

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56432

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Uncertain:1

Oct 17, 2019

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.12389C>T (YP_003024036.1:p.Pro18Leu) variant in MTND5 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PP6, PP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.26
Hmtvar	Pathogenic	0.39
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.37	T
DEOGEN2	Benign	0.081	T
LIST_S2	Benign	0.84	T
MutationAssessor	Pathogenic	3.6	H
PROVEAN	Pathogenic	-6.1	D
Sift4G	Uncertain	0.029	D
GERP RS		3.6
Varity_R		0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603223710; hg19: chrM-12390;