Genetic Variant OGDHL:c.*511G>A (chr10-49734717-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018245.3(OGDHL):c.*511G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,254 control chromosomes in the GnomAD database, including 13,647 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 13628 hom., cov: 33)

Exomes 𝑓: 0.46 ( 19 hom. )

Consequence

OGDHL
NM_018245.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.197

Publications

8 publications found

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]

OGDHL Gene-Disease associations (from GenCC):

Yoon-Bellen neurodevelopmental syndrome
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

OGDHL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018245.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OGDHL	NM_018245.3	MANE Select	c.*511G>A	3_prime_UTR	Exon 23 of 23	NP_060715.2	Q9ULD0-1
OGDHL	NM_001347819.1		c.*511G>A	3_prime_UTR	Exon 23 of 23	NP_001334748.1	Q9ULD0-1
OGDHL	NM_001143996.2		c.*511G>A	3_prime_UTR	Exon 22 of 22	NP_001137468.1	Q9ULD0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OGDHL	ENST00000374103.9	TSL:1 MANE Select	c.*511G>A	3_prime_UTR	Exon 23 of 23	ENSP00000363216.4	Q9ULD0-1
OGDHL	ENST00000852721.1		c.*511G>A	3_prime_UTR	Exon 24 of 24	ENSP00000522780.1
OGDHL	ENST00000852716.1		c.*511G>A	3_prime_UTR	Exon 23 of 23	ENSP00000522775.1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58304

AN:

151972

Hom.:

13630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.869

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.400

GnomAD4 exome

AF:

0.457

AC:

AN:

164

Hom.:

Cov.:

AF XY:

0.489

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.430

AC:

AN:

128

Other (OTH)

AF:

0.700

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.383

AC:

58309

AN:

152090

Hom.:

13628

Cov.:

AF XY:

0.388

AC XY:

28887

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.129

AC:

5347

AN:

41506

American (AMR)

AF:

0.472

AC:

7208

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1141

AN:

3472

East Asian (EAS)

AF:

0.869

AC:

4494

AN:

5170

South Asian (SAS)

AF:

0.414

AC:

1997

AN:

4826

European-Finnish (FIN)

AF:

0.513

AC:

5428

AN:

10584

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.461

AC:

31293

AN:

67946

Other (OTH)

AF:

0.404

AC:

852

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1608

3216

4823

6431

8039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.425

Hom.:

23936

Bravo

AF:

0.375

Asia WGS

AF:

0.615

AC:

2137

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over