M-12349-A-G

Position:

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000361567.2(MT-ND5):ā€‹c.13A>Gā€‹(p.Thr5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Mitomap GenBank:
š‘“ 0.00010 ( AC: 9 )

Consequence

MT-ND5
ENST00000361567.2 missense

Scores

Apogee2
Benign
0.011

Clinical Significance

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

Conservation

PhyloP100: -6.32
Variant links:
Genes affected
MT-ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) 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; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]
MT-TL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Apogee2 supports a benign effect, 0.010796399 < 0.5 .
BS2
High AC in GnomadMitoHomoplasmic at 4

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRNL2TRNL2.1 use as main transcript downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MT-ND5ENST00000361567.2 linkuse as main transcriptc.13A>G p.Thr5Ala missense_variant 1/1 ENSP00000354813 P1
MT-TL2ENST00000387456.1 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:
0.00010
AC:
9
Gnomad homoplasmic
AF:
0.000071
AC:
4
AN:
56433
Gnomad heteroplasmic
AF:
0.000018
AC:
1
AN:
56433

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.12349A>G (YP_003024036.1:p.Thr5Ala) variant in MTND5 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.011
Hmtvar
Benign
0.13
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.54
T
DEOGEN2
Benign
0.016
T
LIST_S2
Benign
0.70
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-0.92
N
Sift4G
Benign
0.16
T
GERP RS
-9.1
Varity_R
0.30

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: rs1603223678; hg19: chrM-12350; API