M-14854-C-T

Variant names:

• chrM-14854-C-T
• rs1057516071
• ENST00000361789.2:c.108C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000361789.2(MT-CYB):​c.108C>T​(p.Leu36Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 10)
• Consequence: MT-CYB ENST00000361789.2 synonymous
• Clinical Significance: Uncertain significance no assertion criteria provided U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -13.9
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomadMitoHomoplasmic at 12

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.108C>T	p.Leu36Leu	synonymous_variant	Exon 1 of 1
ND6	unassigned_transcript_4816	c.-181G>A		upstream_gene_variant
TRNE	unassigned_transcript_4817	c.-112G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.108C>T	p.Leu36Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000354554.2
MT-ND6	ENST00000361681.2	c.-181G>A		upstream_gene_variant		6		ENSP00000354665.2
MT-TE	ENST00000387459.1	n.-112G>A		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00020 AC: 10

Gnomad homoplasmic AF: 0.00021 AC: 12 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Alfa AF: 0.000223 Hom.: 1

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial cytopathy Uncertain:1

Nov 21, 2016

Center for Neuroscience and Cell Biology, University of Coimbra, Portugal

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-14
Mutation Taster		=41/59	disease causing

Other links and lift over

dbSNP: rs1057516071; hg19: chrM-14855;