ENST00000362079.2:c.598G>T

Variant names:

• chrM-9804-G-T
• rs200613617
• ENST00000362079.2:c.598G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The ENST00000362079.2(MT-CO3):​c.598G>T​(p.Ala200Ser) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A200T) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 1)
• Consequence: MT-CO3 ENST00000362079.2 missense
• Scores: Apogee2 Benign 0.30
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 4.01
• Publications: 11 publications found

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]

TRNG (HGNC:7486): (mitochondrially encoded tRNA glycine)

TRNG Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.30258596 < 0.5 .
• BS2: High AC in GnomadMitoHomoplasmic at 4

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000362079.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CO3	ENST00000362079.2	TSL:6	c.598G>T	p.Ala200Ser	missense	Exon 1 of 1	ENSP00000354982.2
	MT-TG	ENST00000387429.1	TSL:6	n.-187G>T		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 1

Gnomad homoplasmic AF: 0.000071 AC: 4 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Uncertain:1

Oct 17, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.9804G>T (YP_003024032.1:p.Ala200Ser) 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 v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.30
Hmtvar	Benign	0.30
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.33	T
DEOGEN2	Benign	0.082	T
LIST_S2	Benign	0.63	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.0
PROVEAN	Uncertain	-2.5	D
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.021	D
GERP RS		4.3
Varity_R		0.44
Mutation Taster		=39/61	disease causing

Other links and lift over

dbSNP: rs200613617; hg19: chrM-9805;