M-14470-T-C

Variant names:

• chrM-14470-T-C
• rs3135030
• ENST00000361681.2:c.204A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The ENST00000361681.2(MT-ND6):​c.204A>G​(p.Gly68Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G68G) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.019 (AC: 1137)
• Consequence: MT-ND6 ENST00000361681.2 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -4.43
• Publications: 16 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: Benign. The variant received -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=-4.43 with no splicing effect.
• BA1: High frequency in mitomap database: 0.0186

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND6	unassigned_transcript_4816	c.204A>G	p.Gly68Gly	synonymous_variant	Exon 1 of 1
TRNE	unassigned_transcript_4817	c.*204A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND6	ENST00000361681.2	c.204A>G	p.Gly68Gly	synonymous_variant	Exon 1 of 1	6		ENSP00000354665.2
MT-TE	ENST00000387459.1	n.*204A>G		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.019 AC: 1137

Gnomad homoplasmic AF: 0.016 AC: 882 AN: 56411

Gnomad heteroplasmic AF: 0.00012 AC: 7 AN: 56411

Alfa AF: 0.00901 Hom.: 102

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs3135030; hg19: chrM-14471;