rs587776438

Positions:

• chrM-10254-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000361227.2(MT-ND3):​c.196G>A​(p.Asp66Asn) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-ND3 ENST00000361227.2 missense
• Scores: Apogee2 Pathogenic 0.92
• Clinical Significance: not provided no classification provided O:1 Leigh-Disease
• Conservation: PhyloP100: 7.79

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP3: Apogee2 supports a deletorius effect, 0.92485976 >= 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND3	ENST00000361227.2	c.196G>A	p.Asp66Asn	missense_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap

Leigh-Disease

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Leigh syndrome Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.92
Hmtvar	Pathogenic	0.81
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.088	D
DEOGEN2	Pathogenic	0.84	D
LIST_S2	Uncertain	0.95	D
MutationAssessor	Pathogenic	3.9	H
MutationTaster	Benign	0.000040	A
PROVEAN	Pathogenic	-4.8	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
GERP RS		5.1
Varity_R		0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs587776438; hg19: chrM-10255;