M-8616-G-T

Position:

• chrM-8616-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0035 (AC: 213)
• Consequence: ATP6 missense
• Scores: Apogee2 Benign 0.15
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.25

Genes affected

ATP6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant M-8616-G-T is Benign according to our data. Variant chrM-8616-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 235626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 324

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6	unassigned_transcript_4806	c.90G>T	p.Leu30Phe	missense_variant	1/1
ATP8	unassigned_transcript_4805	c.*44G>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0035 AC: 213

Gnomad homoplasmic AF: 0.0057 AC: 324 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Alfa AF: 0.00446 Hom.: 20

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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.8616G>T (YP_003024031.1:p.Leu30Phe) variant in MTATP6 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2 -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Oct 13, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.15
Hmtvar	Pathogenic	0.76
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
DEOGEN2	Benign	0.055	T
LIST_S2	Benign	0.73	T
MutationAssessor	Benign	1.6	L
PROVEAN	Uncertain	-3.2	D
Sift4G	Uncertain	0.043	D
GERP RS		-7.5
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: rs41427749; hg19: chrM-8617;