rs1556423787

Variant names:

• chrM-10237-T-C
• rs1556423787
• unassigned_transcript_4808:c.179T>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0016 (AC: 100)
• Consequence: ND3 missense
• Scores: Apogee2 Pathogenic 0.67
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1 LHON
• Conservation: PhyloP100: 7.73

Genes affected

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]

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)

COX3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

TRNG (HGNC:7486): (mitochondrially encoded tRNA glycine)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-10237-T-C is Benign according to our data. Variant chrM-10237-T-C is described in ClinVar as [Benign]. Clinvar id is 65508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 101

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND3	unassigned_transcript_4808	c.179T>C	p.Ile60Thr	missense_variant	Exon 1 of 1
ND4L	unassigned_transcript_4810	c.-233T>C		upstream_gene_variant
TRNR	unassigned_transcript_4809	c.-168T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0016 AC: 100

Gnomad homoplasmic AF: 0.0018 AC: 101 AN: 56415

Gnomad heteroplasmic AF: 0.00016 AC: 9 AN: 56415

Alfa AF: 0.000557 Hom.: 2

Mitomap

LHON

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Oct 17, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.10237T>C (YP_003024033.1:p.Ile60Thr) variant in MTND3 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2 -

Leber optic atrophy Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.67
Hmtvar	Pathogenic	0.77
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.090	T
DEOGEN2	Uncertain	0.74	D
LIST_S2	Benign	0.78	T
MutationAssessor	Pathogenic	3.2	M
PROVEAN	Pathogenic	-4.7	D
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
GERP RS		5.1
Varity_R		0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556423787; hg19: chrM-10238; COSMIC: COSV104668802; COSMIC: COSV104668802;