chrM-10609-T-C

Position:

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBA1

The ENST00000361335.1(MT-ND4L):ā€‹c.140T>Cā€‹(p.Met47Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Mitomap GenBank:
š‘“ 0.023 ( AC: 1432 )

Consequence

MT-ND4L
ENST00000361335.1 missense

Scores

Apogee2
Benign
0.016

Clinical Significance

Benign criteria provided, single submitter B:1
Type-2-diabetes-patients-with-underlying-3243G-/-LHON-patient-with-10663C

Conservation

PhyloP100: -0.299
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 Benign. Variant got -11 ACMG points.

BP4
Apogee2 supports a benign effect, 0.016342986 < 0.5 .
BP6
Variant M-10609-T-C is Benign according to our data. Variant chrM-10609-T-C is described in ClinVar as [Benign]. Clinvar id is 693302.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
High frequency in mitomap database: 0.0234

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.140T>C p.Met47Thr 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:
0.023
AC:
1432
Gnomad homoplasmic
AF:
0.0037
AC:
208
AN:
56425
Gnomad heteroplasmic
AF:
0.000018
AC:
1
AN:
56425
Alfa
AF:
0.00475
Hom.:
186

Mitomap

Type-2-diabetes-patients-with-underlying-3243G-/-LHON-patient-with-10663C

ClinVar

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

Submissions by phenotype

Leigh syndrome Benign:1
Benign, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineOct 17, 2019The NC_012920.1:m.10609T>C (YP_003024034.1:p.Met47Thr) variant in MTND4L gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BA1 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.016
Hmtvar
Benign
0.11
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.58
T
MutationTaster
Benign
1.0
N
GERP RS
-3.4
Varity_R
0.055

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: rs200487531; hg19: chrM-10610; API