rs1057516069

Variant names:

• chrM-14563-C-T
• rs1057516069
• ENST00000361681.2:c.111G>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.111G>A​(p.Val37Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 8)
• Consequence: MT-ND6 ENST00000361681.2 synonymous
• Clinical Significance: Uncertain significance no assertion criteria provided U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -20.0
• Publications: 0 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]

MT-CYB (HGNC:7427): (mitochondrially encoded cytochrome b) Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including electron transport coupled proton transport; response to cobalamin; and response to glucagon. Located in mitochondrion. Implicated in ovarian carcinoma and urinary bladder cancer. [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=-20 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND6	unassigned_transcript_4816	c.111G>A	p.Val37Val	synonymous_variant	Exon 1 of 1
CYTB	unassigned_transcript_4818	c.-184C>T		upstream_gene_variant
TRNE	unassigned_transcript_4817	c.*111G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND6	ENST00000361681.2	c.111G>A	p.Val37Val	synonymous_variant	Exon 1 of 1	6		ENSP00000354665.2
MT-CYB	ENST00000361789.2	c.-184C>T		upstream_gene_variant		6		ENSP00000354554.2
MT-TE	ENST00000387459.1	n.*111G>A		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00010 AC: 8

Gnomad homoplasmic AF: 0.00016 AC: 9 AN: 56433

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56433

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial cytopathy Uncertain:1

Nov 21, 2016

Center for Neuroscience and Cell Biology, University of Coimbra, Portugal

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-20
Mutation Taster		=95/5	polymorphism

Other links and lift over

dbSNP: rs1057516069; hg19: chrM-14564;