Variant 7-44624504-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_002541.4(OGDH):c.161G>A(p.Ser54Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OGDH
NM_002541.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=0.22467154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGDH	NM_002541.4 linkuse as main transcript	c.161G>A	p.Ser54Asn	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.161G>A	p.Ser54Asn	missense_variant	2/23	1	NM_002541.4	ENSP00000222673.5		Q02218-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.161G>A (p.S54N) alteration is located in exon 2 (coding exon 1) of the OGDH gene. This alteration results from a G to A substitution at nucleotide position 161, causing the serine (S) at amino acid position 54 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0069

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

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.0030

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

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

M_CAP

Benign

0.0076

MetaRNN

Benign

0.22

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.60

.;N;.;N;.;.;.;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.84

N;N;N;N;N;N;.;N

REVEL

Benign

0.057

Sift

Benign

0.24

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

Sift4G

Benign

0.30

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

Polyphen

0.0

B;.;B;.;.;.;.;B

Vest4

0.40

MutPred

0.63

Loss of disorder (P = 0.0952);Loss of disorder (P = 0.0952);Loss of disorder (P = 0.0952);Loss of disorder (P = 0.0952);Loss of disorder (P = 0.0952);Loss of disorder (P = 0.0952);Loss of disorder (P = 0.0952);Loss of disorder (P = 0.0952);

MVP

0.31

MPC

0.29

ClinPred

0.62

GERP RS

4.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.31

gMVP

0.58

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over