M-4612-T-C

Position:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Mitomap GenBank:
𝑓 0.00030 ( AC: 21 )

Consequence

ND2
missense

Scores

Apogee2
Benign
0.024

Clinical Significance

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

Conservation

PhyloP100: 0.00300
Variant links:
Genes affected
ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) 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; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6
Variant M-4612-T-C is Benign according to our data. Variant chrM-4612-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 692467.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomadMitoHomoplasmic at 12

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ND2unassigned_transcript_4793 c.143T>C p.Ile48Thr missense_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt

Frequencies

GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
0.00030
AC:
21
Gnomad homoplasmic
AF:
0.00021
AC:
12
AN:
56433
Gnomad heteroplasmic
AF:
0.000018
AC:
1
AN:
56433
Alfa
AF:
0.000231
Hom.:
1

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.4612T>C (YP_003024027.1:p.Met48Thr) variant in MTND2 gene is interpretated to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.024
Hmtvar
Benign
0.21
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.58
T
GERP RS
-8.7
Varity_R
0.061

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: rs1603219525; hg19: chrM-4613; API