M-8411-A-G

Position:

• chrM-8411-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000361851.1(MT-ATP8):​c.46A>G​(p.Met16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 2)
• Consequence: MT-ATP8 ENST00000361851.1 missense
• Scores: Apogee2 Benign 0.076
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 Severe-mitochondrial-disorder
• Conservation: PhyloP100: 0.789

Genes affected

ATP8 (HGNC:):

MT-ATP8 (HGNC:7415): (mitochondrially encoded ATP synthase 8) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in multiple sclerosis and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-TK (HGNC:7489): (mitochondrially encoded tRNA lysine)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.076371066 < 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8	ATP8.1	c.46A>G	p.Met16Val	missense_variant	1/1		YP_003024030.1
TRNK	TRNK.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ATP8	ENST00000361851.1	c.46A>G	p.Met16Val	missense_variant	1/1			ENSP00000355265	P1
MT-TK	ENST00000387421.1			downstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0 AC: 2

Gnomad homoplasmic AF: 0.000053 AC: 3 AN: 56432

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56432

Mitomap

Severe-mitochondrial-disorder

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Oct 17, 2019

The NC_012920.1:m.8411A>G (YP_003024030.1:p.Met16Val) variant in MTATP8 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PM9, PP4, PP6 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.076
Hmtvar	Pathogenic	0.48
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.23	T
MutationTaster	Benign	1.0	N
GERP RS		0.45
Varity_R		0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs878942289; hg19: chrM-8412;