M-8403-T-C

Position:

• chrM-8403-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The ENST00000361851.1(MT-ATP8):​c.38T>C​(p.Ile13Thr) variant causes a missense change involving the alteration of a 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 0.00010 (AC: 4)
• Consequence: MT-ATP8 ENST00000361851.1 missense
• Scores: Apogee2 Benign 0.24
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 Episodic-weakness-and-progressive-neuropathy
• Conservation: PhyloP100: 7.70

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.2386181 < 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8	ATP8.1	c.38T>C	p.Ile13Thr	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.38T>C	p.Ile13Thr	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: 0.00010 AC: 4

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56433

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56433

Alfa AF: 0.000223 Hom.: 1

Mitomap

Episodic-weakness-and-progressive-neuropathy

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.8403T>C (YP_003024030.1:p.Ile13Thr) 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, PP6, PP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.24
Hmtvar	Pathogenic	0.83
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.17	T
DEOGEN2	Benign	0.28	T
LIST_S2	Benign	0.77	T
MutationTaster	Benign	1.0	N
PROVEAN	Pathogenic	-5.0	D
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.017	D
GERP RS		5.0
Varity_R		0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603221460; hg19: chrM-8404;