rs1057516075

Variant names:

• chrM-15246-G-A
• rs1057516075
• ENST00000361789.2:c.500G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000361789.2(MT-CYB):​c.500G>A​(p.Gly167Asp) variant causes a missense change. In-silico tool predicts a pathogenic 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. G167S) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Pathogenic 0.56
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1 Mitochondrial-Respiratory-Chain-Disorder
• Conservation: PhyloP100: 6.20
• Publications: 2 publications found

Genes affected

MT-CYB (HGNC:7427): (mitochondrially encoded cytochrome b) Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including electron transport coupled proton transport; response to cobalamin; and response to glucagon. Located in mitochondrion. Implicated in ovarian carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-CYB Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP3: Apogee2 supports a deletorius effect, 0.5643136 >= 0.5 .

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361789.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CYB	ENST00000361789.2	TSL:6	c.500G>A	p.Gly167Asp	missense	Exon 1 of 1	ENSP00000354554.2

Frequencies

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56418

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56418

Mitomap

Disease(s): Mitochondrial-Respiratory-Chain-Disorder

Status: Reported

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Developmental delay;C1384666:Hearing impairment;C2243051:Macrocephaly (1)
-	1	-	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.56
Hmtvar	Pathogenic	0.88
AlphaMissense	Uncertain	0.36
PhyloP100		6.2

Other links and lift over

dbSNP: rs1057516075; hg19: chrM-15247;