M-14753-CCA-ACT

Variant names:

• chrM-14753-CCA-ACT
• ENST00000361789.2:c.7_9delCCAinsACT
• MT-CYB p.Pro3Thr

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000361789.2(MT-CYB):​c.7_9delCCAinsACT​(p.Pro3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3S) has been classified as Benign.

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CYB ENST00000361789.2 missense
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: 1.55
• Publications: 0 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-ND6 (HGNC:7462): (mitochondrially encoded NADH dehydrogenase 6) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy; Leigh disease; and spinal muscular atrophy with lower extremity predominante 2B. [provided by Alliance of Genome Resources, Apr 2022]

TRNE (HGNC:7479): (mitochondrially encoded tRNA glutamic acid)

TRNE Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CYB	ENST00000361789.2	TSL:6	c.7_9delCCAinsACT	p.Pro3Thr	missense	N/A	ENSP00000354554.2	P00156
	MT-ND6	ENST00000361681.2	TSL:6	c.-82_-80delTGGinsAGT		upstream_gene	N/A	ENSP00000354665.2	P03923
	MT-TE	ENST00000387459.1	TSL:6	n.-13_-11delTGGinsAGT		upstream_gene	N/A

Frequencies

Mitomap GenBank The variant is not present, suggesting it is rare .

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrM-14754;