rs199476114

Variant names:

• chrM-10664-C-A
• rs193302933
• ENST00000361335.1:c.195C>A

Your query was ambiguous. Multiple possible variants found:

• chrM-10664-C-A
• chrM-10664-C-T

Variant summary

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

The ENST00000361335.1(MT-ND4L):​c.195C>A​(p.Val65Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 2)
• Consequence: MT-ND4L ENST00000361335.1 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -2.72
• Publications: 5 publications found

Genes affected

MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [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]

TRNR (HGNC:7496): (mitochondrially encoded tRNA arginine)

TRNR 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=-2.72 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND4L	unassigned_transcript_4810	c.195C>A	p.Val65Val	synonymous_variant	Exon 1 of 1
ND4	unassigned_transcript_4811	c.-96C>A		upstream_gene_variant
TRNR	unassigned_transcript_4809	c.*195C>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND4L	ENST00000361335.1	c.195C>A	p.Val65Val	synonymous_variant	Exon 1 of 1	6		ENSP00000354728.1
MT-ND4	ENST00000361381.2	c.-96C>A		upstream_gene_variant		6		ENSP00000354961.2
MT-TR	ENST00000387439.1	n.*195C>A		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0 AC: 2

Gnomad homoplasmic AF: 0.000035 AC: 2 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.7
Mutation Taster		=77/23	polymorphism

Other links and lift over

dbSNP: rs193302933; hg19: chrM-10665;