rs879192165

Variant names:

• chrM-14692-A-G
• rs879192165
• unassigned_transcript_4817:c.51T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The ENST00000000000(TRNE):​c.51T>C​(p.Val17Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★★).

• Frequency: Mitomap GenBank: 𝑓 0.00040 (AC: 25)
• Consequence: TRNE ENST00000000000 synonymous
• Scores: Mitotip Benign 2.0
• Clinical Significance: Uncertain significance reviewed by expert panel P:2 U:1 LHON-helper-/-Maternally-inherited-diabetes-&-deafness-/tic-disorder
• Conservation: PhyloP100: 1.86
• 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 -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=1.86 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387459.1. 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-TE	ENST00000387459.1	TSL:6	n.51T>C		non_coding_transcript_exon	Exon 1 of 1
	MT-CYB	ENST00000361789.2	TSL:6	c.-55A>G		upstream_gene	N/A	ENSP00000354554.2	P00156
	MT-ND6	ENST00000361681.2	TSL:6	c.-19T>C		upstream_gene	N/A	ENSP00000354665.2	P03923

Frequencies

Mitomap GenBank AF: 0.00040 AC: 25

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56434

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56434

Mitomap

Disease(s): LHON-helper-/-Maternally-inherited-diabetes-&-deafness-/tic-disorder

Status: Reported

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
1	1	-	Mitochondrial disease (2)
1	-	-	Diabetes-deafness syndrome maternally transmitted (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.0
Hmtvar	Benign	0.10
PhyloP100		1.9
Mutation Taster		=99/1	polymorphism

Other links and lift over

dbSNP: rs879192165; hg19: chrM-14693;