M-8414-C-T

Position:

• chrM-8414-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The ENST00000361851.1(MT-ATP8):​c.49C>T​(p.Leu17Phe) 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L17P) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.038 (AC: 2307)
• Consequence: MT-ATP8 ENST00000361851.1 missense
• Scores: Apogee2 Benign 0.062
• Clinical Significance: Benign criteria provided, single submitter B:1 Increased-risk-of-T2DM-and-high-altitude-polycythemia-(HAPC)-in-haplogroup-D4-/-Longevity
• Conservation: PhyloP100: -0.243

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 Benign. Variant got -11 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.062326487 < 0.5 .
• BP6: Variant M-8414-C-T is Benign according to our data. Variant chrM-8414-C-T is described in ClinVar as [Benign]. Clinvar id is 692850.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.0377

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8	ATP8.1	c.49C>T	p.Leu17Phe	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.49C>T	p.Leu17Phe	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: 0.038 AC: 2307

Gnomad homoplasmic AF: 0.0090 AC: 507 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Alfa AF: 0.00995 Hom.: 392

Mitomap

Increased-risk-of-T2DM-and-high-altitude-polycythemia-(HAPC)-in-haplogroup-D4-/-Longevity

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Benign, 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.8414C>T (YP_003024030.1:p.Leu17Phe) variant in MTATP8 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.062
Hmtvar	Pathogenic	0.71
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
DEOGEN2	Benign	0.032	T
LIST_S2	Benign	0.69	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-2.0	N
Sift	Benign	0.44	T
Sift4G	Benign	0.15	T
GERP RS		-9.6
Varity_R		0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28358884; hg19: chrM-8415;