M-15615-G-A

Position:

• chrM-15615-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

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

• Frequency: Mitomap GenBank: Absent
• Consequence: CYTB missense
• Scores: Apogee2 Pathogenic 0.97
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2 EXIT-/-Antimycin-resistance
• Conservation: PhyloP100: 9.28

Genes affected

CYTB (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-15615-G-A is Pathogenic according to our data. Variant chrM-15615-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 9678.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYTB	unassigned_transcript_4819	c.869G>A	p.Gly290Asp	missense_variant	1/1

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

EXIT-/-Antimycin-resistance

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial myopathy with reversible cytochrome C oxidase deficiency Pathogenic:1

Likely pathogenic, 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.15615G>A (YP_003024038.1:p.Gly290Asp) variant in MTCYB gene is interpretated to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PM8, PM10, PP6, PP7 -

Exercise intolerance Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 30, 1999

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.97
Hmtvar	Pathogenic	0.86
AlphaMissense	Pathogenic	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs207459997; hg19: chrM-15616;