chrM-10161-A-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000361227.2(MT-ND3):c.103A>T(p.Thr35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Mitomap GenBank:
𝑓 0.0 ( AC: 0 )
Consequence
MT-ND3
ENST00000361227.2 missense
ENST00000361227.2 missense
Scores
Apogee2
Benign
Clinical Significance
No linked disesase in Mitomap
Conservation
PhyloP100: 1.95
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very low frequency in mitomap database: 0.0
BP4
Apogee2 supports a benign effect, 0.060099766 < 0.5 .
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MT-ND3 | ENST00000361227.2 | c.103A>T | p.Thr35Ser | missense_variant | 1/1 | 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:
0
Gnomad homoplasmic
AF:
AC:
0
AN:
56433
Gnomad heteroplasmic
AF:
AC:
1
AN:
56433
Mitomap
No disease associated.
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mitochondrial disease Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Feb 15, 2022 | The m.10161A>T variant in the mitochondrial genome has not previously been reported in the literature nor public variant repositories (ClinVar and LOVD). It has been observed in one individual at 63% heteroplasmy level in gnomAD v3.1.2 dataset while it is absent in MitoMap database, suggesting it is not a common benign variant in the populations represented in those databases. The m.10161A>T variant is located in MT-ND3, and is predicted to replace a threonine amino acid with serine at codon 35 (p.(Thr35Ser)). This variant was detected at 25.8% heteroplasmy level (1307/5054reads) in this individual and at 11% heteroplasmy level (649/5859reads) in their mother. The affected residue (p.Thr35) is not evolutionarily conserved, and in silico predictions are not in favor of damaging effect (APOGEE score = 0.3); however, there are no functional studies to support or refute these predictions. A nearby m.10158T>C p.(Ser34Pro) variant has been curated as pathogenic for primary mitochondrial disease including Leigh syndrome by ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel (ClinVar ID: 9714). Based on available evidence this maternally inherited mitochondrial m.10161A>T p.(Thr35Ser) variant identified in MT-ND3 is classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
Hmtvar
Benign
AlphaMissense
Benign
BayesDel_addAF
Benign
T
DEOGEN2
Benign
T
LIST_S2
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PROVEAN
Benign
N
Sift
Benign
T
Sift4G
Benign
T
GERP RS
Varity_R
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.