rs1057516067

Variant names:

• chrM-12013-A-G
• rs1057516067
• ENST00000361381.2:c.1254A>G
• MT-ND4 p.Ser418Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The ENST00000361381.2(MT-ND4):​c.1254A>G​(p.Ser418Ser) 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 0.0 (AC: 0)
• Consequence: MT-ND4 ENST00000361381.2 synonymous
• Clinical Significance: Uncertain significance no assertion criteria provided U:4 No linked disesase in Mitomap
• Conservation: PhyloP100: -1.68
• Publications: 0 publications found

Genes affected

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]

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: DEFINITIVE Submitted by: ClinGen

ACMG classification

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

• PM2: Very low frequency in mitomap database: 0.0
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361381.2. 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-ND4	ENST00000361381.2	TSL:6	c.1254A>G	p.Ser418Ser	synonymous	Exon 1 of 1	ENSP00000354961.2	P03905
	MT-TH	ENST00000387441.1	TSL:6	n.-125A>G		upstream_gene	N/A
	MT-TS2	ENST00000387449.1	TSL:6	n.-194A>G		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56432

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56432

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental delay;C1384666:Hearing impairment;C1391997:Congenital cardiomyopathy;C4551563:Microcephaly (1)
-	1	-	Developmental delay;C1384666:Hearing impairment;C2243051:Macrocephaly (1)
-	1	-	Epilepsy;C0026827:Hypotonia;C0085584:Encephalopathy;C0424605:Developmental delay;C0497327:Dementia;na:Calcification of extrapyramidal basal ganglia (1)
-	1	-	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7
Mutation Taster		=88/12	polymorphism

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1057516067;

hg19: chrM-12014;