7-44624507-C-T

Position:

chr7-44624507-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_002541.4(OGDH):c.164C>T(p.Ser55Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00824 in 1,613,744 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0084 ( 74 hom. )

Consequence

OGDH
NM_002541.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.79

Variant links:

Genes affected

OGDH (HGNC:8124): (oxoglutarate dehydrogenase) This gene encodes one subunit of the 2-oxoglutarate dehydrogenase complex. This complex catalyzes the overall conversion of 2-oxoglutarate (alpha-ketoglutarate) to succinyl-CoA and CO(2) during the Krebs cycle. The protein is located in the mitochondrial matrix and uses thiamine pyrophosphate as a cofactor. A congenital deficiency in 2-oxoglutarate dehydrogenase activity is believed to lead to hypotonia, metabolic acidosis, and hyperlactatemia. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

OGDH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), OGDH. . Gene score misZ 4.7595 (greater than the threshold 3.09). Trascript score misZ 5.6536 (greater than threshold 3.09). GenCC has associacion of gene with oxoglutaricaciduria.

BP4

Computational evidence support a benign effect (MetaRNN=0.008775711).

BP6

Variant 7-44624507-C-T is Benign according to our data. Variant chr7-44624507-C-T is described in ClinVar as [Benign]. Clinvar id is 780042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGDH	NM_002541.4 linkuse as main transcript	c.164C>T	p.Ser55Leu	missense_variant	2/23	ENST00000222673.6	NP_002532.2	Q02218-1B4E3E9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGDH	ENST00000222673.6 linkuse as main transcript	c.164C>T	p.Ser55Leu	missense_variant	2/23	1	NM_002541.4	ENSP00000222673.5		Q02218-1

Frequencies

GnomAD3 genomes

AF:

0.00650

AC:

986

AN:

151770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.00565

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00541

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.00683

AC:

1716

AN:

251406

Hom.:

AF XY:

0.00701

AC XY:

952

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.00595

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.00587

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.00842

AC:

12311

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

6034

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00525

Gnomad4 ASJ exome

AF:

0.00635

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.00689

Gnomad4 NFE exome

AF:

0.00971

Gnomad4 OTH exome

AF:

0.00773

GnomAD4 genome

AF:

0.00649

AC:

986

AN:

151888

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

469

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.00564

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00541

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.00932

Hom.:

Bravo

AF:

0.00665

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00895

AC:

ExAC

AF:

0.00726

AC:

882

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0112

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Oxoglutaricaciduria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

OGDH: BS1, BS2 -

OGDH-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

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

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0079

T;.;.;.;T;T;T;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0088

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.0

.;M;.;M;.;.;.;M

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.0

N;D;D;D;D;D;.;D

REVEL

Benign

0.24

Sift

Uncertain

0.0020

D;D;D;D;D;D;.;D

Sift4G

Benign

0.073

T;T;D;D;D;D;D;D

Polyphen

0.20

B;.;P;.;.;.;.;P

Vest4

0.68

MVP

0.59

MPC

0.47

ClinPred

0.025

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.76

gMVP

0.72

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