rs7090775

Positions:

• chr10-49751919-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018245.3(OGDHL):​c.657G>A​(p.Gln219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,614,154 control chromosomes in the GnomAD database, including 1,427 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.040 (169 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1258 hom.)
• Consequence: OGDHL NM_018245.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=2.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGDHL	NM_018245.3	c.657G>A	p.Gln219=	synonymous_variant	6/23	ENST00000374103.9	NP_060715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGDHL	ENST00000374103.9	c.657G>A	p.Gln219=	synonymous_variant	6/23	1	NM_018245.3	ENSP00000363216	P1
OGDHL	ENST00000419399.4	c.486G>A	p.Gln162=	synonymous_variant	5/22	2		ENSP00000401356
OGDHL	ENST00000432695.2	c.30G>A	p.Gln10=	synonymous_variant	4/21	2		ENSP00000390240

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6052 AN: 152200 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0289

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0368

GnomAD3 exomes AF: 0.0368 AC: 9264 AN: 251466 Hom.: 285 AF XY: 0.0401 AC XY: 5454 AN XY: 135910

Gnomad AFR exome AF: 0.0645

Gnomad AMR exome AF: 0.0195

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.00332

Gnomad SAS exome AF: 0.0972

Gnomad FIN exome AF: 0.0240

Gnomad NFE exome AF: 0.0310

Gnomad OTH exome AF: 0.0393

GnomAD4 exome AF: 0.0364 AC: 53199 AN: 1461836 Hom.: 1258 Cov.: 33 AF XY: 0.0379 AC XY: 27539 AN XY: 727218

Gnomad4 AFR exome AF: 0.0612

Gnomad4 AMR exome AF: 0.0207

Gnomad4 ASJ exome AF: 0.0206

Gnomad4 EAS exome AF: 0.00184

Gnomad4 SAS exome AF: 0.0927

Gnomad4 FIN exome AF: 0.0243

Gnomad4 NFE exome AF: 0.0337

Gnomad4 OTH exome AF: 0.0407

GnomAD4 genome AF: 0.0399 AC: 6084 AN: 152318 Hom.: 169 Cov.: 32 AF XY: 0.0400 AC XY: 2978 AN XY: 74492

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.0288

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0340 Hom.: 54

Bravo AF: 0.0401

Asia WGS AF: 0.0600 AC: 210 AN: 3478

EpiCase AF: 0.0310

EpiControl AF: 0.0351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	9.8
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs7090775; hg19: chr10-50959965; COSMIC: COSV65103824; COSMIC: COSV65103824;