M-9219-T-G

Position:

• chrM-9219-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: COX3 missense
• Scores: Apogee2 Benign 0.019
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 1.81

Genes affected

COX3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BS2: High AC in GnomadMitoHomoplasmic at 4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX3	unassigned_transcript_4807	c.13T>G	p.Ser5Ala	missense_variant	1/1
ATP6	unassigned_transcript_4806	c.*12T>G		downstream_gene_variant

Ensembl

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

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0 AC: 3

Gnomad homoplasmic AF: 0.000071 AC: 4 AN: 56433

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56433

Alfa AF: 0.000668 Hom.: 3

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Uncertain:1

Uncertain significance, 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.9219T>G (YP_003024032.1:p.Ser5Ala) variant in MTCO3 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.019
Hmtvar	Benign	0.040
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.39	T
DEOGEN2	Benign	0.017	T
LIST_S2	Benign	0.35	T
MutationAssessor	Benign	-0.84	N
PROVEAN	Benign	-0.85	N
Sift	Uncertain	0.0050	D
Sift4G	Benign	1.0	T
GERP RS		0.51
Varity_R		0.14

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603222184; hg19: chrM-9220;