rs200911567

Positions:

• chrM-11984-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361381.2(MT-ND4):​c.1225T>C​(p.Tyr409His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0010 (AC: 63)
• Consequence: MT-ND4 ENST00000361381.2 missense
• Scores: Apogee2 Benign 0.15
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1 Leigh-Syndrome
• Conservation: PhyloP100: -0.0180

Genes affected

MT-ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.15468292 < 0.5 .
• BP6: Variant M-11984-T-C is Benign according to our data. Variant chrM-11984-T-C is described in ClinVar as [Benign]. Clinvar id is 155888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 55

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ND4	ENST00000361381.2	c.1225T>C	p.Tyr409His	missense_variant	1/1			ENSP00000354961	P1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0010 AC: 63

Gnomad homoplasmic AF: 0.00097 AC: 55 AN: 56431

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56431

Alfa AF: 0.000381 Hom.: 15

Mitomap

Leigh-Syndrome

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1 Other: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.11984T>C (YP_003024035.1:p.Tyr409His) 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: BS1, BS4, BP4 -
not provided, no classification provided	literature only	GeneReviews	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.15
Hmtvar	Pathogenic	0.76
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.49	T
DEOGEN2	Benign	0.12	T
LIST_S2	Benign	0.67	T
MutationAssessor	Benign	0.51	N
MutationTaster	Benign	8.6e-8	A
PROVEAN	Uncertain	-2.7	D
Sift	Benign	0.30	T
Sift4G	Benign	0.24	T
GERP RS		1.4
Varity_R		0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200911567; hg19: chrM-11985;