Variant rs2853826 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBA1

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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T114I) has been classified as Uncertain significance.

Frequency

Mitomap GenBank:

𝑓 0.42 ( AC: 25902 )

Consequence

MT-ND3
ENST00000361227.2 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

Variant links:

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-ND3 links:

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

MT-TR links:

TRNR (HGNC:):

TRNR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 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_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
TRNR	TRNR.1 use as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ND3	ENST00000361227.2 linkuse as main transcript	c.340A>G	p.Thr114Ala	missense_variant	1/1			ENSP00000355206	P1
MT-TR	ENST00000387439.1 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD4 exome

Cov.:

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:

AN:

56170

Alfa

AF:

0.169

Hom.:

6166

Mitomap

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 -

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

LIST_S2

Uncertain

0.96

MutationAssessor

Benign

-0.60

MutationTaster

Benign

1.0

PROVEAN

Benign

-1.4

Sift

Benign

0.41

Sift4G

Benign

1.0

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Mitomap

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over