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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361681.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND6	ENST00000361681.2	TSL:6	c.192G>A	p.Met64Met	synonymous	Exon 1 of 1	ENSP00000354665.2
	MT-TE	ENST00000387459.1	TSL:6	n.*192G>A		downstream_gene	N/A

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 v4.9

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;