rs28359178
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PS1_ModerateBP4BP6_ModerateBA1
The ENST00000361567.2(MT-ND5):c.1372G>A(p.Ala458Thr) 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 Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.
Frequency
Mitomap GenBank:
𝑓 0.075 ( AC: 4560 )
Consequence
MT-ND5
ENST00000361567.2 missense
ENST00000361567.2 missense
Scores
Apogee2
Benign
Clinical Significance
LHON-/-Increased-MS-risk-/-higher-freq-in-PD-ADS
Conservation
PhyloP100: 0.633
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PS1
?
Transcript ENST00000361567.2 (MT-ND5) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
BP4
?
Apogee2 supports a benign effect, 0.30702576 < 0.5 .
BP6
?
Variant M-13708-G-A is Benign according to our data. Variant chrM-13708-G-A is described in ClinVar as [Benign]. Clinvar id is 9696.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
High frequency in mitomap database: 0.0746
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MT-ND5 | ENST00000361567.2 | c.1372G>A | p.Ala458Thr | missense_variant | 1/1 | P1 |
Frequencies
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
AC:
4560
Gnomad homoplasmic
AF:
AC:
4263
AN:
56361
Gnomad heteroplasmic
AF:
AC:
21
AN:
56361
Alfa
AF:
Hom.:
Mitomap
LHON-/-Increased-MS-risk-/-higher-freq-in-PD-ADS
ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Leber optic atrophy Pathogenic:1Uncertain:1
Uncertain significance, no assertion criteria provided | curation | GeneReviews | Sep 19, 2013 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 30, 1992 | - - |
Leigh syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Oct 17, 2019 | The NC_012920.1:m.13708G>A (YP_003024036.1:p.Ala458Thr) variant in MTND5 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:
Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
Hmtvar
Benign
AlphaMissense
Benign
BayesDel_addAF
Benign
T
DEOGEN2
Benign
T
LIST_S2
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PROVEAN
Benign
N
Sift4G
Benign
T
GERP RS
Varity_R
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at