rs878853060

chrM-9861-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000362079.2(MT-CO3):c.655T>C(p.Phe219Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0021 (AC: 127)
• Consequence: MT-CO3 ENST00000362079.2 missense
• Scores: Apogee2 Benign 0.041
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 AD
• Conservation: PhyloP100: -0.824

Genes affected

COX3 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.0412673 < 0.5 .
• BP6: Variant M-9861-T-C is Benign according to our data. Variant chrM-9861-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 235537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 120

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX3	COX3.1	c.655T>C	p.Phe219Leu	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CO3	ENST00000362079.2	c.655T>C	p.Phe219Leu	missense_variant	1/1			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: 0.0021 AC: 127

Gnomad homoplasmic AF: 0.0021 AC: 120 AN: 56410

Gnomad heteroplasmic AF: 0.00012 AC: 7 AN: 56410

Alfa AF: 0.00223 Hom.: 10

Mitomap

AD

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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.9861T>C (YP_003024032.1:p.Phe219Leu) 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: BS1, BS2 -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 12, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.041
Hmtvar	Benign	0.10
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.51	T
DEOGEN2	Benign	0.011	T
LIST_S2	Benign	0.53	T
MutationAssessor	Benign	-1.8	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	2.7	N
Sift	Benign	0.069	T
Sift4G	Benign	1.0	T
GERP RS		-3.3
Varity_R		0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs878853060; hg19: chrM-9862;