rs200873900

Positions:

• chrM-11696-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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

• Frequency: Mitomap GenBank: 𝑓 0.0060 (AC: 365)
• Consequence: ND4 missense
• Scores: Apogee2 Benign 0.34
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 O:1 LHON-/-LDYT-/-DEAF-/-hypertension-helper-mut.
• Conservation: PhyloP100: 1.12

Genes affected

ND4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant M-11696-G-A is Benign according to our data. Variant chrM-11696-G-A is described in ClinVar as [Benign]. Clinvar id is 9710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: High frequency in mitomap database: 0.006
• BS2: High AC in GnomadMitoHomoplasmic at 56

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ND4	unassigned_transcript_4812	c.937G>A	p.Val313Ile	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: 0.0060 AC: 365

Gnomad homoplasmic AF: 0.00099 AC: 56 AN: 56427

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56427

Alfa AF: 0.00125 Hom.: 49

Mitomap

LHON-/-LDYT-/-DEAF-/-hypertension-helper-mut.

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leber optic atrophy and dystonia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 22, 2003

- -

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.11696G>A (YP_003024035.1:p.Val313Ile) variant in MTND4 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BA1 -

Leber optic atrophy Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.34
Hmtvar	Benign	0.12
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.45	T
DEOGEN2	Benign	0.013	T
LIST_S2	Benign	0.29	T
MutationAssessor	Benign	-1.1	N
PROVEAN	Benign	-0.32	N
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
GERP RS		0.49
Varity_R		0.13

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200873900; hg19: chrM-11697;