rs200911567

Positions:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The ENST00000361381.2(MT-ND4):ā€‹c.1225T>Cā€‹(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 (ā˜…).

Frequency

Mitomap GenBank:
š‘“ 0.0010 ( AC: 63 )

Consequence

MT-ND4
ENST00000361381.2 missense

Scores

Apogee2
Benign
0.15

Clinical Significance

Benign criteria provided, single submitter B:1O:1
Leigh-Syndrome

Conservation

PhyloP100: -0.0180
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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-ND4ENST00000361381.2 linkuse as main transcriptc.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:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Leigh syndrome Benign:1Other:1
Benign, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineOct 17, 2019The 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 providedliterature onlyGeneReviews-- -

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200911567; hg19: chrM-11985; API