NM_018245.3:c.2381A>T

Variant names:

• chr10-49738201-T-A
• rs1196658326
• NM_018245.3:c.2381A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018245.3(OGDHL):​c.2381A>T​(p.Asp794Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OGDHL NM_018245.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGDHL	NM_018245.3	c.2381A>T	p.Asp794Val	missense_variant	Exon 18 of 23	ENST00000374103.9	NP_060715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGDHL	ENST00000374103.9	c.2381A>T	p.Asp794Val	missense_variant	Exon 18 of 23	1	NM_018245.3	ENSP00000363216.4
OGDHL	ENST00000419399.4	c.2210A>T	p.Asp737Val	missense_variant	Exon 17 of 22	2		ENSP00000401356.1
OGDHL	ENST00000432695.2	c.1754A>T	p.Asp585Val	missense_variant	Exon 16 of 21	2		ENSP00000390240.1
OGDHL	ENST00000490844.1	n.1299A>T		non_coding_transcript_exon_variant	Exon 1 of 5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251458 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135900

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461776 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727204

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.2	D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.95	P;P;P
Vest4		0.89
MutPred		0.44		Loss of disorder (P = 0.0105);.;.;
MVP		0.42
MPC		0.48
ClinPred		0.96	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.66
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1196658326; hg19: chr10-50946247;