M-14482-C-T

Variant names:

• chrM-14482-C-T
• rs199476108
• ENST00000361681.2:c.192G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP7 BS2

The ENST00000361681.2(MT-ND6):​c.192G>A​(p.Met64Met) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.00040 (AC: 23)
• Consequence: MT-ND6 ENST00000361681.2 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -3.83
• Publications: 15 publications found

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]

TRNE (HGNC:7479): (mitochondrially encoded tRNA glutamic acid)

TRNE Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 80

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND6	unassigned_transcript_4816	c.192G>A	p.Met64Met	synonymous_variant	Exon 1 of 1
TRNE	unassigned_transcript_4817	c.*192G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND6	ENST00000361681.2	c.192G>A	p.Met64Met	synonymous_variant	Exon 1 of 1	6		ENSP00000354665.2
MT-TE	ENST00000387459.1	n.*192G>A		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00040 AC: 23

Gnomad homoplasmic AF: 0.0014 AC: 80 AN: 56433

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56433

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
DEOGEN2	Benign	0.33	T
LIST_S2	Benign	0.73	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-3.8
PROVEAN	Benign	-1.3	N
Sift	Uncertain	0.0060	D
GERP RS		-0.73
Varity_R		0.47
Mutation Taster		=79/21	polymorphism

Other links and lift over

dbSNP: rs199476108; hg19: chrM-14483;