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10-49737844-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_018245.3(OGDHL):c.2532A>C(p.Thr844=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,614,004 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0015 ( 8 hom. )

Consequence

OGDHL
NM_018245.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.762
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 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=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-49737844-T-G is Benign according to our data. Variant chr10-49737844-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3040480.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=-0.762 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OGDHLNM_018245.3 linkuse as main transcriptc.2532A>C p.Thr844= synonymous_variant 20/23 ENST00000374103.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OGDHLENST00000374103.9 linkuse as main transcriptc.2532A>C p.Thr844= synonymous_variant 20/231 NM_018245.3 P1Q9ULD0-1
OGDHLENST00000419399.4 linkuse as main transcriptc.2361A>C p.Thr787= synonymous_variant 19/222 Q9ULD0-2
OGDHLENST00000432695.2 linkuse as main transcriptc.1905A>C p.Thr635= synonymous_variant 18/212 Q9ULD0-3
OGDHLENST00000490844.1 linkuse as main transcriptn.1568A>C non_coding_transcript_exon_variant 2/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00141
AC:
215
AN:
152020
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.0804
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00270
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00160
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00129
AC:
325
AN:
251478
Hom.:
1
AF XY:
0.00148
AC XY:
201
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.000492
Gnomad AMR exome
AF:
0.000347
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00307
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00170
Gnomad OTH exome
AF:
0.00277
GnomAD4 exome
AF:
0.00149
AC:
2183
AN:
1461866
Hom.:
8
Cov.:
31
AF XY:
0.00154
AC XY:
1119
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00304
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.00160
Gnomad4 OTH exome
AF:
0.00139
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00141
AC:
215
AN:
152138
Hom.:
1
Cov.:
33
AF XY:
0.00148
AC XY:
110
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00270
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.00160
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00166
Hom.:
1
Bravo
AF:
0.00161
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00240
EpiControl
AF:
0.00314

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 submitterclinical testingPreventionGenetics, part of Exact SciencesSep 25, 2019This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
4.2
Dann
Benign
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs41281971; hg19: chr10-50945890; API