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GeneBe

10-49735330-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_018245.3(OGDHL):c.2931G>A(p.Ala977=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,613,470 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0080 ( 14 hom., cov: 33)
Exomes 𝑓: 0.00083 ( 23 hom. )

Consequence

OGDHL
NM_018245.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.78
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=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-49735330-C-T is Benign according to our data. Variant chr10-49735330-C-T is described in ClinVar as [Benign]. Clinvar id is 719468.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=-3.78 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00805 (1226/152350) while in subpopulation AFR AF= 0.0271 (1127/41580). AF 95% confidence interval is 0.0258. There are 14 homozygotes in gnomad4. There are 576 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OGDHLNM_018245.3 linkuse as main transcriptc.2931G>A p.Ala977= synonymous_variant 23/23 ENST00000374103.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OGDHLENST00000374103.9 linkuse as main transcriptc.2931G>A p.Ala977= synonymous_variant 23/231 NM_018245.3 P1Q9ULD0-1
OGDHLENST00000419399.4 linkuse as main transcriptc.2760G>A p.Ala920= synonymous_variant 22/222 Q9ULD0-2
OGDHLENST00000432695.2 linkuse as main transcriptc.2304G>A p.Ala768= synonymous_variant 21/212 Q9ULD0-3
OGDHLENST00000490844.1 linkuse as main transcriptn.1967G>A non_coding_transcript_exon_variant 5/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00788
AC:
1200
AN:
152234
Hom.:
11
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0266
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00550
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00203
AC:
509
AN:
250754
Hom.:
5
AF XY:
0.00148
AC XY:
201
AN XY:
135502
show subpopulations
Gnomad AFR exome
AF:
0.0281
Gnomad AMR exome
AF:
0.00130
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000984
GnomAD4 exome
AF:
0.000832
AC:
1215
AN:
1461120
Hom.:
23
Cov.:
32
AF XY:
0.000700
AC XY:
509
AN XY:
726874
show subpopulations
Gnomad4 AFR exome
AF:
0.0282
Gnomad4 AMR exome
AF:
0.00172
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.00257
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00805
AC:
1226
AN:
152350
Hom.:
14
Cov.:
33
AF XY:
0.00773
AC XY:
576
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.0271
Gnomad4 AMR
AF:
0.00549
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00271
Hom.:
2
Bravo
AF:
0.00940
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
0.53
Dann
Benign
0.59

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: rs113014306; hg19: chr10-50943376; COSMIC: COSV65102268; API