chrM-14748-T-C

Variant names:

• chrM-14748-T-C
• rs1603224852
• ENST00000361789.2:c.2T>C

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The ENST00000361789.2(MT-CYB):​c.2T>C​(p.Met1?) variant causes a start lost change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-CYB ENST00000361789.2 start_lost
• Scores: Apogee2 Benign 0.22
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 7.15
• 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: Pathogenic. The variant received 10 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very low frequency in mitomap database: 0.0

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.2T>C	p.Met1?	start_lost	Exon 1 of 1	ENSP00000354554.2	P00156
	MT-ND6	ENST00000361681.2	TSL:6	c.-75A>G		upstream_gene	N/A	ENSP00000354665.2	P03923
	MT-TE	ENST00000387459.1	TSL:6	n.-6A>G		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 0

Alfa AF: 0.000111 Hom.: 0

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.22
Hmtvar	Pathogenic	0.73
PhyloP100		7.2
Mutation Taster		=35/165	disease causing

Other links and lift over

dbSNP: rs1603224852; hg19: chrM-14749;