chrM-14470-T-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BP7 BS2

The ENST00000361681.2(MT-ND6):​c.204A>T​(p.Gly68Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0038 (AC: 234)
• Consequence: MT-ND6 ENST00000361681.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 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 -13 ACMG points.

• BP6: Variant M-14470-T-A is Benign according to our data. Variant chrM-14470-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 235574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.43 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 337

Transcripts

RefSeq

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

Ensembl

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

Frequencies

Mitomap GenBank AF: 0.0038 AC: 234

Gnomad homoplasmic AF: 0.0060 AC: 337 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Alfa AF: 0.00329 Hom.: 102

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 29, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.4
Mutation Taster		=79/21	polymorphism

Other links and lift over

dbSNP: rs3135030; hg19: chrM-14471;