10-49736505-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_018245.3(OGDHL):c.2606G>A(p.Arg869Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,613,270 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
OGDHL
NM_018245.3 missense
NM_018245.3 missense
Scores
7
7
5
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.824
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OGDHL | NM_018245.3 | c.2606G>A | p.Arg869Gln | missense_variant | 21/23 | ENST00000374103.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OGDHL | ENST00000374103.9 | c.2606G>A | p.Arg869Gln | missense_variant | 21/23 | 1 | NM_018245.3 | P1 | |
OGDHL | ENST00000419399.4 | c.2435G>A | p.Arg812Gln | missense_variant | 20/22 | 2 | |||
OGDHL | ENST00000432695.2 | c.1979G>A | p.Arg660Gln | missense_variant | 19/21 | 2 | |||
OGDHL | ENST00000490844.1 | n.1642G>A | non_coding_transcript_exon_variant | 3/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152166Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.0000321 AC: 8AN: 248914Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134806
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461104Hom.: 0 Cov.: 34 AF XY: 0.0000344 AC XY: 25AN XY: 726886
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2022 | The c.2606G>A (p.R869Q) alteration is located in exon 21 (coding exon 20) of the OGDHL gene. This alteration results from a G to A substitution at nucleotide position 2606, causing the arginine (R) at amino acid position 869 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Benign
T;T;D
Sift4G
Benign
T;T;T
Polyphen
D;D;D
Vest4
MutPred
Loss of sheet (P = 0.0817);.;.;
MVP
MPC
ClinPred
D
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