chr10-49736114-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_018245.3(OGDHL):c.2818G>A(p.Ala940Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00129 in 1,612,092 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0047 ( 7 hom., cov: 33)
Exomes 𝑓: 0.00093 ( 6 hom. )
Consequence
OGDHL
NM_018245.3 missense
NM_018245.3 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 3.92
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010488629).
BP6
?
Variant 10-49736114-C-T is Benign according to our data. Variant chr10-49736114-C-T is described in ClinVar as [Benign]. Clinvar id is 3043968.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00469 (715/152298) while in subpopulation AFR AF= 0.0143 (593/41566). AF 95% confidence interval is 0.0133. There are 7 homozygotes in gnomad4. There are 306 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OGDHL | NM_018245.3 | c.2818G>A | p.Ala940Thr | missense_variant | 22/23 | ENST00000374103.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OGDHL | ENST00000374103.9 | c.2818G>A | p.Ala940Thr | missense_variant | 22/23 | 1 | NM_018245.3 | P1 | |
OGDHL | ENST00000419399.4 | c.2647G>A | p.Ala883Thr | missense_variant | 21/22 | 2 | |||
OGDHL | ENST00000432695.2 | c.2191G>A | p.Ala731Thr | missense_variant | 20/21 | 2 | |||
OGDHL | ENST00000490844.1 | n.1854G>A | non_coding_transcript_exon_variant | 4/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00470 AC: 715AN: 152180Hom.: 7 Cov.: 33
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GnomAD3 exomes AF: 0.00146 AC: 363AN: 248424Hom.: 4 AF XY: 0.00115 AC XY: 154AN XY: 134184
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GnomAD4 exome AF: 0.000931 AC: 1359AN: 1459794Hom.: 6 Cov.: 34 AF XY: 0.000865 AC XY: 628AN XY: 726120
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
OGDHL-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 04, 2019 | This variant is classified as 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
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
B;B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
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