rs200487531

Variant names:

• chrM-10609-T-C
• rs200487531
• unassigned_transcript_4810:c.140T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency: Mitomap GenBank: 𝑓 0.023 (AC: 1432)
• Consequence: ND4L missense
• Scores: Apogee2 Benign 0.016
• Clinical Significance: Benign criteria provided, single submitter B:1 Type-2-diabetes-patients-with-underlying-3243G-/-LHON-patient-with-10663C
• Conservation: PhyloP100: -0.299

Genes affected

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]

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]

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]

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant M-10609-T-C is Benign according to our data. Variant chrM-10609-T-C is described in ClinVar as [Benign]. Clinvar id is 693302.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.0234

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND4L	unassigned_transcript_4810	c.140T>C	p.Ile47Thr	missense_variant	Exon 1 of 1
ND4	unassigned_transcript_4811	c.-151T>C		upstream_gene_variant
ND3	unassigned_transcript_4808	c.*205T>C		downstream_gene_variant
TRNR	unassigned_transcript_4809	c.*140T>C		downstream_gene_variant

Ensembl

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

Frequencies

Mitomap GenBank AF: 0.023 AC: 1432

Gnomad homoplasmic AF: 0.0037 AC: 208 AN: 56425

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56425

Alfa AF: 0.00423 Hom.: 215

Mitomap

Disease(s): Type-2-diabetes-patients-with-underlying-3243G-/-LHON-patient-with-10663C

Status: Reported

ClinVar

Significance: Benign

Submissions summary: Benign: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.10609T>C (YP_003024034.1:p.Met47Thr) variant in MTND4L gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.016
Hmtvar	Benign	0.11
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.58	T
PhyloP100		-0.30
GERP RS		-3.4
Varity_R		0.055
Mutation Taster		=100/0	polymorphism

Publications

LitVar

Other links and lift over

dbSNP: rs200487531; hg19: chrM-10610;