M-12406-G-A

Position:

• chrM-12406-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency: Mitomap GenBank: 𝑓 0.026 (AC: 1614)
• Consequence: ND5 missense
• Scores: Apogee2 Benign 0.017
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -1.37

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant M-12406-G-A is Benign according to our data. Variant chrM-12406-G-A is described in ClinVar as [Benign]. Clinvar id is 693436.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.026400002

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ND5	unassigned_transcript_4815	c.70G>A	p.Val24Ile	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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: 0.026 AC: 1614

Gnomad homoplasmic AF: 0.0088 AC: 497 AN: 56422

Gnomad heteroplasmic AF: 0.00018 AC: 10 AN: 56422

Alfa AF: 0.00342 Hom.: 28

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Oct 17, 2019

The NC_012920.1:m.12406G>A (YP_003024036.1:p.Val24Ile) variant in MTND5 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished).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: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.017
Hmtvar	Benign	0.060
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.57	T
DEOGEN2	Benign	0.0032	T
LIST_S2	Benign	0.45	T
MutationAssessor	Benign	-0.36	N
PROVEAN	Benign	-0.39	N
Sift4G	Benign	0.50	T
GERP RS		-8.8
Varity_R		0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28617389; hg19: chrM-12407;