rs1057516062

chrM-8418-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The ENST00000361851.1(MT-ATP8):c.53T>C(p.Leu18Pro) 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: 1)
• Consequence: MT-ATP8 ENST00000361851.1 missense
• Scores: Apogee2 Benign 0.17
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1 Mitochondrial-Respiratory-Chain-Disorder
• Conservation: PhyloP100: 1.65

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.17495258 < 0.5 .
• BS2: High AC in GnomadMitoHomoplasmic at 4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8	ATP8.1	c.53T>C	p.Leu18Pro	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ATP8	ENST00000361851.1	c.53T>C	p.Leu18Pro	missense_variant	1/1			P1

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: 1

Gnomad homoplasmic AF: 0.000071 AC: 4 AN: 56432

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56432

Mitomap

Mitochondrial-Respiratory-Chain-Disorder

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Optic neuropathy Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

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

Nov 21, 2016

- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.17
Hmtvar	Pathogenic	0.77
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.35	T
DEOGEN2	Benign	0.098	T
LIST_S2	Benign	0.58	T
MutationTaster	Benign	1.0	N
PROVEAN	Uncertain	-3.8	D
Sift	Benign	0.14	T
Sift4G	Benign	0.19	T
GERP RS		2.7
Varity_R		0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057516062; hg19: chrM-8419;