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GeneBe

10-49736483-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_018245.3(OGDHL):c.2628C>T(p.Ala876=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,613,706 control chromosomes in the GnomAD database, including 1,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 93 hom., cov: 33)
Exomes 𝑓: 0.037 ( 1190 hom. )

Consequence

OGDHL
NM_018245.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.80
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-49736483-G-A is Benign according to our data. Variant chr10-49736483-G-A is described in ClinVar as [Benign]. Clinvar id is 3056267.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.8 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OGDHLNM_018245.3 linkuse as main transcriptc.2628C>T p.Ala876= synonymous_variant 21/23 ENST00000374103.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OGDHLENST00000374103.9 linkuse as main transcriptc.2628C>T p.Ala876= synonymous_variant 21/231 NM_018245.3 P1Q9ULD0-1
OGDHLENST00000419399.4 linkuse as main transcriptc.2457C>T p.Ala819= synonymous_variant 20/222 Q9ULD0-2
OGDHLENST00000432695.2 linkuse as main transcriptc.2001C>T p.Ala667= synonymous_variant 19/212 Q9ULD0-3
OGDHLENST00000490844.1 linkuse as main transcriptn.1664C>T non_coding_transcript_exon_variant 3/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0276
AC:
4204
AN:
152130
Hom.:
93
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00702
Gnomad AMI
AF:
0.0648
Gnomad AMR
AF:
0.0302
Gnomad ASJ
AF:
0.0884
Gnomad EAS
AF:
0.000773
Gnomad SAS
AF:
0.0286
Gnomad FIN
AF:
0.0109
Gnomad MID
AF:
0.0570
Gnomad NFE
AF:
0.0403
Gnomad OTH
AF:
0.0340
GnomAD3 exomes
AF:
0.0306
AC:
7670
AN:
250264
Hom.:
177
AF XY:
0.0315
AC XY:
4268
AN XY:
135350
show subpopulations
Gnomad AFR exome
AF:
0.00630
Gnomad AMR exome
AF:
0.0205
Gnomad ASJ exome
AF:
0.0917
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0289
Gnomad FIN exome
AF:
0.0142
Gnomad NFE exome
AF:
0.0401
Gnomad OTH exome
AF:
0.0356
GnomAD4 exome
AF:
0.0369
AC:
53955
AN:
1461458
Hom.:
1190
Cov.:
35
AF XY:
0.0371
AC XY:
26948
AN XY:
727050
show subpopulations
Gnomad4 AFR exome
AF:
0.00747
Gnomad4 AMR exome
AF:
0.0220
Gnomad4 ASJ exome
AF:
0.0904
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0293
Gnomad4 FIN exome
AF:
0.0153
Gnomad4 NFE exome
AF:
0.0399
Gnomad4 OTH exome
AF:
0.0366
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0276
AC:
4202
AN:
152248
Hom.:
93
Cov.:
33
AF XY:
0.0264
AC XY:
1964
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00700
Gnomad4 AMR
AF:
0.0301
Gnomad4 ASJ
AF:
0.0884
Gnomad4 EAS
AF:
0.000775
Gnomad4 SAS
AF:
0.0286
Gnomad4 FIN
AF:
0.0109
Gnomad4 NFE
AF:
0.0403
Gnomad4 OTH
AF:
0.0336
Alfa
AF:
0.0389
Hom.:
66
Bravo
AF:
0.0279
Asia WGS
AF:
0.0130
AC:
45
AN:
3478
EpiCase
AF:
0.0441
EpiControl
AF:
0.0452

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 submitterclinical testingPreventionGenetics, part of Exact SciencesMar 27, 2019This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
0.038
Dann
Benign
0.43
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs12357255; hg19: chr10-50944529; COSMIC: COSV65103265; API