M-10602-A-G

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000361335.1(MT-ND4L):ā€‹c.133A>Gā€‹(p.Thr45Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Mitomap GenBank:
š‘“ 0.0 ( AC: 0 )

Consequence

MT-ND4L
ENST00000361335.1 missense

Scores

Apogee2
Benign
0.010

Clinical Significance

Uncertain significance criteria provided, single submitter U:1
No linked disesase in Mitomap

Conservation

PhyloP100: -8.35
Variant links:
Genes affected
MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very low frequency in mitomap database: 0.0
BP4
Apogee2 supports a benign effect, 0.010189079 < 0.5 .

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-ND4LENST00000361335.1 linkuse as main transcriptc.133A>G p.Thr45Ala missense_variant 1/1 ENSP00000354728 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:
0.0
AC:
0
Gnomad homoplasmic
AF:
0.000018
AC:
1
AN:
56430
Gnomad heteroplasmic
AF:
0.0
AC:
0
AN:
56430

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Leigh syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineOct 17, 2019The NC_012920.1:m.10602A>G (YP_003024034.1:p.Thr45Ala) variant in MTND4L gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PP7, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.010
Hmtvar
Benign
0.12
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.47
T
DEOGEN2
Benign
0.032
T
LIST_S2
Benign
0.65
T
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-1.7
N
Sift
Benign
0.14
T
Sift4G
Benign
0.30
T
GERP RS
-10
Varity_R
0.13

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: rs1603222913; hg19: chrM-10603; API