M-4512-G-A

Position:

• chrM-4512-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

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

• Frequency: Mitomap GenBank: 𝑓 0.00040 (AC: 27)
• Consequence: ND2 missense
• Scores: Apogee2 Benign 0.047
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -9.81

Genes affected

ND2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-4512-G-A is Benign according to our data. Variant chrM-4512-G-A is described in ClinVar as [Benign]. Clinvar id is 692457.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 19

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ND2	unassigned_transcript_4794	c.43G>A	p.Ala15Thr	missense_variant	1/1
TRNM	unassigned_transcript_4793	c.*43G>A		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: 0.00040 AC: 27

Gnomad homoplasmic AF: 0.00034 AC: 19 AN: 56427

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56427

Alfa AF: 0.000449 Hom.: 2

Mitomap

No disease associated.

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.4512G>A (YP_003024027.1:p.Ala15Thr) variant in MTND2 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.047
Hmtvar	Benign	0.13
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.50	T
DEOGEN2	Benign	0.016	T
LIST_S2	Benign	0.52	T
MutationAssessor	Benign	-1.3	N
PROVEAN	Benign	0.15	N
Sift4G	Benign	0.31	T
GERP RS		-8.4
Varity_R		0.11

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603219492; hg19: chrM-4513;