M-14225-C-T

Position:

• chrM-14225-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The ENST00000361681.2(MT-ND6):​c.449G>A​(p.Arg150His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R150C) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 8)
• Consequence: MT-ND6 ENST00000361681.2 missense
• Scores: Apogee2 Benign 0.13
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.212

Genes affected

MT-ND6 (HGNC:7462): (mitochondrially encoded NADH dehydrogenase 6) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy; Leigh disease; and spinal muscular atrophy with lower extremity predominante 2B. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.1320393 < 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ND6	ENST00000361681.2	c.449G>A	p.Arg150His	missense_variant	1/1			ENSP00000354665	P1

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: 8

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56434

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56434

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Uncertain:1

Uncertain significance, 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.14225C>T (YP_003024037.1:p.Arg150His) variant in MTND6 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: no criteria -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.13
Hmtvar	Pathogenic	0.62
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
DEOGEN2	Benign	0.24	T
LIST_S2	Benign	0.45	T
MutationAssessor	Benign	1.2	L
PROVEAN	Benign	0.020	N
Sift	Benign	0.10	T
Sift4G	Benign	0.37	T
GERP RS		-5.9
Varity_R		0.051

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603224611; hg19: chrM-14226;