chr10-49736482-C-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_018245.3(OGDHL):c.2629G>T(p.Ala877Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,613,754 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0020 ( 7 hom. )
Consequence
OGDHL
NM_018245.3 missense
NM_018245.3 missense
Scores
1
1
17
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
OGDHL (HGNC:25590): (oxoglutarate dehydrogenase L) The protein encoded by this gene is similar to oxoglutarate dehydrogenase (OGDH) of the OGDH complex, which degrades glucose and glutamate. This gene encodes several isoforms, including some that appear to localize to mitochondria. The encoded protein down-regulates the AKT signaling cascade and can suppress the growth of cervical cancer cells. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.016435802).
BP6
?
Variant 10-49736482-C-A is Benign according to our data. Variant chr10-49736482-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041207.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OGDHL | NM_018245.3 | c.2629G>T | p.Ala877Ser | missense_variant | 21/23 | ENST00000374103.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OGDHL | ENST00000374103.9 | c.2629G>T | p.Ala877Ser | missense_variant | 21/23 | 1 | NM_018245.3 | P1 | |
OGDHL | ENST00000419399.4 | c.2458G>T | p.Ala820Ser | missense_variant | 20/22 | 2 | |||
OGDHL | ENST00000432695.2 | c.2002G>T | p.Ala668Ser | missense_variant | 19/21 | 2 | |||
OGDHL | ENST00000490844.1 | n.1665G>T | non_coding_transcript_exon_variant | 3/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00113 AC: 172AN: 152194Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00162 AC: 405AN: 250296Hom.: 3 AF XY: 0.00166 AC XY: 225AN XY: 135362
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GnomAD4 exome AF: 0.00204 AC: 2985AN: 1461442Hom.: 7 Cov.: 34 AF XY: 0.00194 AC XY: 1409AN XY: 727068
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GnomAD4 genome ? AF: 0.00112 AC: 171AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000967 AC XY: 72AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
OGDHL-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 19, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at