rs2853826

Positions:

• chrM-10398-A-G
• chrM-10398-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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

• Frequency: Mitomap GenBank: 𝑓 0.42 (AC: 25902)
• Consequence: ND3 missense
• Scores: Apogee2 Benign 0.040
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 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

ND3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• 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_multiple_submitters_no_conflicts, 2 stars.
• BA1: High frequency in mitomap database: 0.42369998

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ND3	unassigned_transcript_4809	c.340A>G	p.Thr114Ala	missense_variant	1/1
TRNR	unassigned_transcript_4810	c.-7A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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: 0.42 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:3

Revision: criteria provided, multiple submitters, no conflicts

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.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 -

Parkinson disease, resistance to Benign:1

protective, no assertion criteria provided

literature only

OMIM

Feb 01, 2007

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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
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;