ENST00000361227.2:c.252G>C

Variant names:

• chrM-10310-G-C
• rs41467651
• ENST00000361227.2:c.252G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP7 BS2

The ENST00000361227.2(MT-ND3):​c.252G>C​(p.Leu84Leu) 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 0.00030 (AC: 17)
• Consequence: MT-ND3 ENST00000361227.2 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -11.5
• Publications: 0 publications found

Genes affected

MT-ND3 (HGNC:7458): (mitochondrially encoded NADH dehydrogenase 3) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

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]

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: Likely_benign. The variant received -5 ACMG points.

• BP7: Synonymous conserved (PhyloP=-11.5 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND3	unassigned_transcript_4808	c.252G>C	p.Leu84Leu	synonymous_variant	Exon 1 of 1
ND4L	unassigned_transcript_4810	c.-160G>C		upstream_gene_variant
TRNR	unassigned_transcript_4809	c.-95G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND3	ENST00000361227.2	c.252G>C	p.Leu84Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000355206.2
MT-ND4L	ENST00000361335.1	c.-160G>C		upstream_gene_variant		6		ENSP00000354728.1
MT-TR	ENST00000387439.1	n.-95G>C		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00030 AC: 17

Gnomad homoplasmic AF: 0.00014 AC: 8 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		-12

Other links and lift over

dbSNP: rs41467651; hg19: chrM-10311;