rs200809063
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBS1BS2
The ENST00000362079.2(MT-CO3):c.760G>A(p.Val254Ile) 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 Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Mitomap GenBank:
𝑓 0.0066 ( AC: 401 )
Consequence
MT-CO3
ENST00000362079.2 missense
ENST00000362079.2 missense
Scores
Apogee2
Benign
Clinical Significance
LHON-possible-helper-variant
Conservation
PhyloP100: 0.0720
Genes affected
MT-CO3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Apogee2 supports a benign effect, 0.039187443 < 0.5 .
BP6
?
Variant M-9966-G-A is Benign according to our data. Variant chrM-9966-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
High frequency in mitomap database: 0.0066000004
BS2
?
High AC in GnomadMitoHomoplasmic at 447
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COX3 | COX3.1 use as main transcript | c.760G>A | p.Val254Ile | missense_variant | 1/1 | ||
TRNG | TRNG.1 use as main transcript | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MT-CO3 | ENST00000362079.2 | c.760G>A | p.Val254Ile | missense_variant | 1/1 | P1 | |||
MT-TG | ENST00000387429.1 | upstream_gene_variant |
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:
401
Gnomad homoplasmic
AF:
AC:
447
AN:
56402
Gnomad heteroplasmic
AF:
AC:
6
AN:
56402
Alfa
AF:
Hom.:
Mitomap
LHON-possible-helper-variant
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
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.9966G>A (YP_003024032.1:p.Val254Ile) variant in MTCO3 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
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Dec 01, 2016 | - - |
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