rs1057516070

Variant names:

• chrM-14706-A-G
• rs1057516070
• unassigned_transcript_4817:c.37T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000000000(TRNE):​c.37T>C​(p.Ser13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 8)
• Consequence: TRNE ENST00000000000 missense
• Scores: Mitotip Benign 1.9
• Clinical Significance: Benign criteria provided, single submitter U:2 B:1 O:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.312
• Publications: 0 publications found

Genes affected

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

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]

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-ND6 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet
• Leber plus disease

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• maternally-inherited Leigh syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• MELAS syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant M-14706-A-G is Benign according to our data. Variant chrM-14706-A-G is described in ClinVar as Benign. ClinVar VariationId is 370060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNE	unassigned_transcript_4817	c.37T>C	p.Ser13Pro	missense_variant	Exon 1 of 1
CYTB	unassigned_transcript_4818	c.-41A>G		upstream_gene_variant
ND6	unassigned_transcript_4816	c.-33T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TE	ENST00000387459.1	n.37T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-CYB	ENST00000361789.2	c.-41A>G		upstream_gene_variant		6		ENSP00000354554.2
MT-ND6	ENST00000361681.2	c.-33T>C		upstream_gene_variant		6		ENSP00000354665.2

Frequencies

Mitomap GenBank AF: 0.00010 AC: 8

Gnomad homoplasmic AF: 0.00012 AC: 7 AN: 56431

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56431

Alfa AF: 0.000445 Hom.: 2

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Uncertain:2 Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental delay 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

- -

Sudden death;C1838993:Episodic vomiting;CN239813:Mild liver congestion 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

- -

MELAS syndrome Benign:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.14706A>G variant in MT-TE gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS4, BP4 -

not provided Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	1.9
Hmtvar	Benign	0.0
PhyloP100		-0.31

Other links and lift over

dbSNP: rs1057516070; hg19: chrM-14707;