Genetic Variant OGDHL:p.Ala876Ala (chr10-49736483-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_018245.3(OGDHL):c.2628C>T(p.Ala876Ala) 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 (no stars).

Frequency

Genomes: 𝑓 0.028 ( 93 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1190 hom. )

Consequence

OGDHL
NM_018245.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided 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]

OGDHL links:

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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 (BayesDel_noAF=-0.88).

BP6

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 no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.8 with no splicing effect.

BA1

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 rank	MANE	Protein	UniProt
OGDHL	NM_018245.3 link	c.2628C>T	p.Ala876Ala	synonymous_variant	Exon 21 of 23	ENST00000374103.9	NP_060715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OGDHL	ENST00000374103.9 link	c.2628C>T	p.Ala876Ala	synonymous_variant	Exon 21 of 23	1	NM_018245.3	ENSP00000363216.4	Q9ULD0-1
OGDHL	ENST00000419399.4 link	c.2457C>T	p.Ala819Ala	synonymous_variant	Exon 20 of 22	2		ENSP00000401356.1	Q9ULD0-2
OGDHL	ENST00000432695.2 link	c.2001C>T	p.Ala667Ala	synonymous_variant	Exon 19 of 21	2		ENSP00000390240.1	Q9ULD0-3
OGDHL	ENST00000490844.1 link	n.1664C>T		non_coding_transcript_exon_variant	Exon 3 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0276

AC:

4204

AN:

152130

Hom.:

Cov.:

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.:

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

AF:

0.0276

AC:

4202

AN:

152248

Hom.:

Cov.:

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.:

Bravo

AF:

0.0279

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0441

EpiControl

AF:

0.0452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

OGDHL-related disorder

Benign:1

Mar 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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: 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over