rs1556423787

chrM-10237-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3 BP6_Moderate BS2

The ENST00000361227.2(MT-ND3):c.179T>C(p.Ile60Thr) 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 Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0016 (AC: 100)
• Consequence: MT-ND3 ENST00000361227.2 missense
• Scores: Apogee2 Pathogenic 0.67
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1 LHON
• Conservation: PhyloP100: 7.73

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 Likely_benign. Variant got -5 ACMG points.

• PP3: Apogee2 supports a deletorius effect, 0.66612965 >= 0.5 .
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND3	ENST00000361227.2	c.179T>C	p.Ile60Thr	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 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

Benign, criteria provided, single submitter

clinical testing

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

Oct 17, 2019

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variant in MTND3 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished).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

not provided, no classification provided

literature only

GeneReviews

-

- -

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
MutationTaster	Benign	0.000012	A
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;