M-10507-C-T

Position:

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The ENST00000361335.1(MT-ND4L):​c.38C>T​(p.Thr13Ile) 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T13A) has been classified as Benign.

Frequency

Mitomap GenBank:
𝑓 0.0 ( AC: 0 )

Consequence

MT-ND4L
ENST00000361335.1 missense

Scores

Apogee2
Benign
0.048

Clinical Significance

Likely benign criteria provided, single submitter B:1
No linked disesase in Mitomap

Conservation

PhyloP100: -1.32
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]
MT-TR (HGNC:7496): (mitochondrially encoded tRNA arginine)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very low frequency in mitomap database: 0.0
BP4
Apogee2 supports a benign effect, 0.04784764 < 0.5 .
BP6
Variant M-10507-C-T is Benign according to our data. Variant chrM-10507-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 693294.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRNRTRNR.1 use as main transcript downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MT-ND4LENST00000361335.1 linkuse as main transcriptc.38C>T p.Thr13Ile missense_variant 1/1 ENSP00000354728 P1
MT-TRENST00000387439.1 linkuse as main transcript downstream_gene_variant

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

Mitomap

No disease associated.

ClinVar

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

Submissions by phenotype

Leigh syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineOct 17, 2019The NC_012920.1:m.10507C>T (YP_003024034.1:p.Thr13Ile) variant in MTND4L gene is interpretated to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.048
Hmtvar
Benign
0.10
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.46
T
DEOGEN2
Benign
0.019
T
LIST_S2
Benign
0.61
T
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-0.56
N
Sift
Benign
0.13
T
Sift4G
Benign
0.95
T
GERP RS
-2.4
Varity_R
0.086

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: rs1603222868; hg19: chrM-10508; API