M-10654-C-T

Position:

Variant summary

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

The ENST00000361335.1(MT-ND4L):​c.185C>T​(p.Ala62Val) 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A62T) has been classified as Benign.

Frequency

Mitomap GenBank:
𝑓 0.00080 ( AC: 49 )

Consequence

MT-ND4L
ENST00000361335.1 missense

Scores

Apogee2
Benign
0.031

Clinical Significance

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

Conservation

PhyloP100: 3.29
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 -7 ACMG points.

BP4
Apogee2 supports a benign effect, 0.031223454 < 0.5 .
BP6
Variant M-10654-C-T is Benign according to our data. Variant chrM-10654-C-T is described in ClinVar as [Benign]. Clinvar id is 693308.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomadMitoHomoplasmic at 25

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.185C>T p.Ala62Val 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:
0.00080
AC:
49
Gnomad homoplasmic
AF:
0.00044
AC:
25
AN:
56432
Gnomad heteroplasmic
AF:
0.000035
AC:
2
AN:
56432
Alfa
AF:
0.000223
Hom.:
1

Mitomap

No disease associated.

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.10654C>T (YP_003024034.1:p.Ala62Val) 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: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.031
Hmtvar
Benign
0.12
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.39
T
DEOGEN2
Benign
0.0096
T
LIST_S2
Benign
0.55
T
MutationTaster
Benign
1.0
N
PROVEAN
Benign
2.1
N
Sift
Benign
0.19
T
Sift4G
Benign
0.25
T
GERP RS
3.0
Varity_R
0.065

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: rs1603222934; hg19: chrM-10655; COSMIC: COSV104668835; COSMIC: COSV104668835; API