M-11013-C-A

Position:

• chrM-11013-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

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: 2)
• Consequence: ND4 missense
• Scores: Apogee2 Benign 0.069
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -3.30

Genes affected

ND4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ND4	unassigned_transcript_4812	c.254C>A	p.Ser85Tyr	missense_variant	1/1

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: 0.0 AC: 2

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.000223 Hom.: 3

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Uncertain:1

Uncertain significance, 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.11013C>A (YP_003024035.1:p.Ser85Tyr) variant in MTND4 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.069
Hmtvar	Benign	0.11
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.43	T
DEOGEN2	Benign	0.024	T
LIST_S2	Benign	0.52	T
MutationAssessor	Benign	1.8	L
PROVEAN	Benign	-2.0	N
Sift	Benign	0.093	T
Sift4G	Benign	0.34	T
GERP RS		-6.0
Varity_R		0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs879244441; hg19: chrM-11014;