rs1057516067

Variant names:

• chrM-12013-A-G
• rs1057516067
• ENST00000361381.2:c.1254A>G

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: 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
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND4	unassigned_transcript_4811	c.1254A>G	p.Ser418Ser	synonymous_variant	Exon 1 of 1
TRNH	unassigned_transcript_4812	c.-125A>G		upstream_gene_variant
TRNS2	unassigned_transcript_4813	c.-194A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND4	ENST00000361381.2	c.1254A>G	p.Ser418Ser	synonymous_variant	Exon 1 of 1	6		ENSP00000354961.2
MT-TH	ENST00000387441.1	n.-125A>G		upstream_gene_variant		6
MT-TS2	ENST00000387449.1	n.-194A>G		upstream_gene_variant		6

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

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: no assertion criteria provided

Submissions by phenotype

Leigh syndrome 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

- -

Developmental delay;C1384666:Hearing impairment;C1391997:Congenital cardiomyopathy;C4551563:Microcephaly 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

- -

Developmental delay;C1384666:Hearing impairment;C2243051:Macrocephaly 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

- -

Epilepsy;C0026827:Hypotonia;C0085584:Encephalopathy;C0424605:Developmental delay;C0497327:Dementia;CN239811:Calcification of extrapyramidal basal ganglia 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		-1.7
Mutation Taster		=88/12	polymorphism

Other links and lift over

dbSNP: rs1057516067; hg19: chrM-12014;