M-12367-A-G

Position:

• chrM-12367-A-G

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 Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 4)
• Consequence: ND5 missense
• Scores: Apogee2 Benign 0.025
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.689

Genes affected

ND5 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-12367-A-G is Benign according to our data. Variant chrM-12367-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 693427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 16

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ND5	unassigned_transcript_4816	c.31A>G	p.Thr11Ala	missense_variant	1/1
TRNL2	unassigned_transcript_4815	c.*31A>G		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: 0.00010 AC: 4

Gnomad homoplasmic AF: 0.00028 AC: 16 AN: 56424

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56424

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Likely 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.12367A>G (YP_003024036.1:p.Thr11Ala) variant in MTND5 gene is interpretated to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.025
Hmtvar	Benign	0.15
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.54	T
DEOGEN2	Benign	0.044	T
LIST_S2	Benign	0.58	T
MutationAssessor	Benign	1.8	L
PROVEAN	Benign	-2.3	N
Sift4G	Benign	0.23	T
GERP RS		-9.1
Varity_R		0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603223696; hg19: chrM-12368;