rs207460003

Positions:

• chrM-15498-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

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

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 15)
• Consequence: CYTB missense
• Scores: Apogee2 Pathogenic 0.63
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1 DEAF-/-Infantile-histiocytoid-cardiomyopathy
• Conservation: PhyloP100: 3.78

Genes affected

CYTB (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomadMitoHomoplasmic at 16

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYTB	unassigned_transcript_4819	c.752G>A	p.Gly251Asp	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 GenBank AF: 0.00020 AC: 15

Gnomad homoplasmic AF: 0.00028 AC: 16 AN: 56408

Gnomad heteroplasmic AF: 0.00012 AC: 7 AN: 56408

Alfa AF: 0.000445 Hom.: 2

Mitomap

DEAF-/-Infantile-histiocytoid-cardiomyopathy

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Histiocytoid cardiomyopathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2000

- -

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.15498G>A (YP_003024038.1:p.Gly251Asp) variant in MTCYB gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PM10, PP4, PP6, BS1, BP5 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.63
Hmtvar	Pathogenic	0.69
AlphaMissense	Uncertain	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs207460003; hg19: chrM-15499; COSMIC: COSV104420728; COSMIC: COSV104420728;