chrM-10237-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS2
The ENST00000361227.2(MT-ND3):āc.179T>Cā(p.Ile60Thr) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I60V) has been classified as Uncertain significance.
Frequency
Mitomap GenBank:
š 0.0016 ( AC: 100 )
Consequence
MT-ND3
ENST00000361227.2 missense
ENST00000361227.2 missense
Scores
Apogee2
Pathogenic
Clinical Significance
LHON
Conservation
PhyloP100: 7.73
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 Likely_benign. Variant got -5 ACMG points.
PP3
Apogee2 supports a deletorius effect, 0.66612965 >= 0.5 .
BP6
Variant M-10237-T-C is Benign according to our data. Variant chrM-10237-T-C is described in ClinVar as [Benign]. Clinvar id is 65508.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomadMitoHomoplasmic at 101
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-ND3 | ENST00000361227.2 | c.179T>C | p.Ile60Thr | missense_variant | 1/1 | ENSP00000355206 | P1 |
Frequencies
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
AC:
100
Gnomad homoplasmic
AF:
AC:
101
AN:
56415
Gnomad heteroplasmic
AF:
AC:
9
AN:
56415
Alfa
AF:
Hom.:
Mitomap
LHON
ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
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.10237T>C (YP_003024033.1:p.Ile60Thr) 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: BS1, BS2 - |
Leber optic atrophy Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Apogee2
Pathogenic
Hmtvar
Pathogenic
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
DEOGEN2
Uncertain
D
LIST_S2
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
A
PROVEAN
Pathogenic
D
Sift
Uncertain
D
Sift4G
Pathogenic
D
GERP RS
Varity_R
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at