chrM-14831-G-A

Variant names:

• chrM-14831-G-A
• rs199795644
• ENST00000361789.2:c.85G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361789.2(MT-CYB):​c.85G>A​(p.Ala29Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A29V) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.0019 (AC: 115)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.013
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1 LHON
• Conservation: PhyloP100: -1.78
• Publications: 12 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: Benign. The variant received -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.013223543 < 0.5 .
• BP6: Variant M-14831-G-A is Benign according to our data. Variant chrM-14831-G-A is described in ClinVar as Benign. ClinVar VariationId is 65517.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 162

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.85G>A	p.Ala29Thr	missense	Exon 1 of 1	ENSP00000354554.2
	MT-ND6	ENST00000361681.2	TSL:6	c.-158C>T		upstream_gene	N/A	ENSP00000354665.2
	MT-TE	ENST00000387459.1	TSL:6	n.-89C>T		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0019 AC: 115

Gnomad homoplasmic AF: 0.0029 AC: 162 AN: 56375

Gnomad heteroplasmic AF: 0.00028 AC: 16 AN: 56375

Alfa AF: 0.00353 Hom.: 79

Mitomap

Disease(s): LHON

Status: Reported

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
-	-	-	Leber optic atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.013
Hmtvar	Benign	0.12
AlphaMissense	Benign	0.082
PhyloP100		-1.8
Mutation Taster		=92/8	polymorphism

Other links and lift over

dbSNP: rs199795644; hg19: chrM-14832;