M-10188-A-G

Position:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The ENST00000361227.2(MT-ND3):ā€‹c.130A>Gā€‹(p.Met44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Mitomap GenBank:
š‘“ 0.00020 ( AC: 15 )

Consequence

MT-ND3
ENST00000361227.2 missense

Scores

Apogee2
Benign
0.020

Clinical Significance

Likely benign criteria provided, single submitter B:1
No linked disesase in Mitomap

Conservation

PhyloP100: -0.215
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Apogee2 supports a benign effect, 0.020464215 < 0.5 .
BP6
Variant M-10188-A-G is Benign according to our data. Variant chrM-10188-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 693269.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomadMitoHomoplasmic at 8

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MT-ND3ENST00000361227.2 linkuse as main transcriptc.130A>G p.Met44Val missense_variant 1/1 ENSP00000355206 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:
0.00020
AC:
15
Gnomad homoplasmic
AF:
0.00014
AC:
8
AN:
56433
Gnomad heteroplasmic
AF:
0.000018
AC:
1
AN:
56433
Alfa
AF:
0.000223
Hom.:
1

Mitomap

No disease associated.

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Leigh syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineOct 17, 2019The NC_012920.1:m.10188A>G (YP_003024033.1:p.Met44Val) variant in MTND3 gene is interpretated to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.020
Hmtvar
Benign
0.12
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.47
T
MutationTaster
Benign
1.0
N
GERP RS
-8.3
Varity_R
0.13

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.

Other links and lift over

dbSNP: rs1603222715; hg19: chrM-10189; API