10-49738065-G-C

Variant names:

• chr10-49738065-G-C
• NM_018245.3:c.2399C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018245.3(OGDHL):​c.2399C>G​(p.Thr800Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OGDHL NM_018245.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.448

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051511765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGDHL	NM_018245.3	c.2399C>G	p.Thr800Ser	missense_variant	Exon 19 of 23	ENST00000374103.9	NP_060715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGDHL	ENST00000374103.9	c.2399C>G	p.Thr800Ser	missense_variant	Exon 19 of 23	1	NM_018245.3	ENSP00000363216.4
OGDHL	ENST00000419399.4	c.2228C>G	p.Thr743Ser	missense_variant	Exon 18 of 22	2		ENSP00000401356.1
OGDHL	ENST00000432695.2	c.1772C>G	p.Thr591Ser	missense_variant	Exon 17 of 21	2		ENSP00000390240.1
OGDHL	ENST00000490844.1	n.1435C>G		non_coding_transcript_exon_variant	Exon 1 of 5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2399C>G (p.T800S) alteration is located in exon 19 (coding exon 18) of the OGDHL gene. This alteration results from a C to G substitution at nucleotide position 2399, causing the threonine (T) at amino acid position 800 to be replaced by a serine (S). 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	Benign	0.064
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.47
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.20	N;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.0	N;N;N
REVEL	Benign	0.046
Sift	Benign	0.82	T;T;T
Sift4G	Benign	0.72	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.27
MutPred		0.38		Gain of disorder (P = 0.0309);.;.;
MVP		0.15
MPC		0.15
ClinPred		0.092	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.26

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.

Other links and lift over

hg19: chr10-50946111;