rs2853826

chrM-10398-A-GchrM-10398-A-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The ENST00000361227.2(MT-ND3):c.340A>G(p.Thr114Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Mitomap GenBank: 𝑓 0.42 (AC: 25902)
• Consequence: MT-ND3 ENST00000361227.2 missense
• Scores: Apogee2 Benign 0.040
• Clinical Significance: Benign criteria provided, single submitter B:2 Invasive-Breast-Cancer-risk-factor-AD-PD-BD-lithium-response-Type-2-DM,PD-protective-factor-/-longevity-/-altered-cell-pH-/-metabolic-syndrome-/-breast-cancer-risk-/-Leigh-Syndrome-risk-/-ADHD-/-cognitive-decline-/-SCA2-age-of-onset-/-Fuchs-endothelial-corneal-dystrophy
• Conservation: PhyloP100: -0.338

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-TR (HGNC:7496): (mitochondrially encoded tRNA arginine)

TRNR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.040168878 < 0.5 .
• BP6: Variant M-10398-A-G is Benign according to our data. Variant chrM-10398-A-G is described in ClinVar as [Benign]. Clinvar id is 9713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.42369998

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNR	TRNR.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND3	ENST00000361227.2	c.340A>G	p.Thr114Ala	missense_variant	1/1			P1
MT-TR	ENST00000387439.1			upstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.42 AC: 25902

Gnomad homoplasmic AF: 0.42 AC: 23506 AN: 56170

Gnomad heteroplasmic AF: 0.00014 AC: 8 AN: 56170

Alfa AF: 0.169 Hom.: 6166

Mitomap

Invasive-Breast-Cancer-risk-factor-AD-PD-BD-lithium-response-Type-2-DM,PD-protective-factor-/-longevity-/-altered-cell-pH-/-metabolic-syndrome-/-breast-cancer-risk-/-Leigh-Syndrome-risk-/-ADHD-/-cognitive-decline-/-SCA2-age-of-onset-/-Fuchs-endothelial-corneal-dystrophy

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Parkinson disease, resistance to Benign:1

protective, no assertion criteria provided

literature only

OMIM

Feb 01, 2007

- -

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.10398A>G (YP_003024033.1:p.Thr114Ala) 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: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.040
Hmtvar	Benign	0.040
AlphaMissense	Benign	0.064
DEOGEN2	Benign	0.18	T
LIST_S2	Uncertain	0.96	D
MutationAssessor	Benign	-0.60	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.4	N
Sift	Benign	0.41	T
Sift4G	Benign	1.0	T

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2853826; hg19: chrM-10399;