M-12386-C-T

Variant names:

• chrM-12386-C-T
• rs1603223709
• ENST00000361567.2:c.50C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000361567.2(MT-ND5):​c.50C>T​(p.Pro17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-ND5 ENST00000361567.2 missense
• Scores: Apogee2 Benign 0.014
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.48
• Publications: 0 publications found

Genes affected

MT-ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNH (HGNC:7487): (mitochondrially encoded tRNA histidine)

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

TRNS2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.013727502 < 0.5 .

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361567.2. 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-ND5	ENST00000361567.2	TSL:6	c.50C>T	p.Pro17Leu	missense	Exon 1 of 1	ENSP00000354813.2	P03915
	MT-ND4	ENST00000361381.2	TSL:6	c.*249C>T		downstream_gene	N/A	ENSP00000354961.2	P03905
	MT-TH	ENST00000387441.1	TSL:6	n.*180C>T		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56430

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56430

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.014
Hmtvar	Benign	0.13
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.54	T
DEOGEN2	Benign	0.019	T
LIST_S2	Benign	0.75	T
MutationAssessor	Benign	-0.86	N
PhyloP100		-2.5
PROVEAN	Benign	3.6	N
Sift4G	Benign	0.84	T
GERP RS		-4.3
Varity_R		0.12

Other links and lift over

dbSNP: rs1603223709; hg19: chrM-12387;