chrM-14249-G-A

Position:

• chrM-14249-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361681.2(MT-ND6):​c.425C>T​(p.Ala142Val) 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 Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00040 (AC: 27)
• Consequence: MT-ND6 ENST00000361681.2 missense
• Scores: Apogee2 Benign 0.040
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 2.40

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 Benign. Variant got -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.03968888 < 0.5 .
• BP6: Variant M-14249-G-A is Benign according to our data. Variant chrM-14249-G-A is described in ClinVar as [Benign]. Clinvar id is 693697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 23

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.425C>T	p.Ala142Val	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: 0.00040 AC: 27

Gnomad homoplasmic AF: 0.00041 AC: 23 AN: 56416

Gnomad heteroplasmic AF: 0.00016 AC: 9 AN: 56416

Alfa AF: 0.000779 Hom.: 3

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.14249G>A (YP_003024037.1:p.Ala142Val) variant in MTND6 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	0.040
Hmtvar	Pathogenic	0.45
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.36	T
DEOGEN2	Benign	0.17	T
LIST_S2	Benign	0.79	T
MutationAssessor	Benign	-0.59	N
PROVEAN	Benign	2.1	N
Sift	Benign	0.26	T
Sift4G	Benign	1.0	T
GERP RS		-0.70
Varity_R		0.078

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556424407; hg19: chrM-14250;