NM_018245.3:c.657G>A

Variant names:

• chr10-49751919-C-T
• rs7090775
• NM_018245.3:c.657G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018245.3(OGDHL):​c.657G>A​(p.Gln219Gln) 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
• Publications: 6 publications found

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]

OGDHL Gene-Disease associations (from GenCC):

• Yoon-Bellen neurodevelopmental syndrome

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OGDHL	NM_018245.3	c.657G>A	p.Gln219Gln	synonymous_variant	Exon 6 of 23	ENST00000374103.9	NP_060715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGDHL	ENST00000374103.9	c.657G>A	p.Gln219Gln	synonymous_variant	Exon 6 of 23	1	NM_018245.3	ENSP00000363216.4
OGDHL	ENST00000419399.4	c.486G>A	p.Gln162Gln	synonymous_variant	Exon 5 of 22	2		ENSP00000401356.1
OGDHL	ENST00000432695.2	c.30G>A	p.Gln10Gln	synonymous_variant	Exon 4 of 21	2		ENSP00000390240.1

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

GnomAD2 exomes AF: 0.0368 AC: 9264 AN: 251466 AF XY: 0.0401

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 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

African (AFR) AF: 0.0612 AC: 2048 AN: 33480

American (AMR) AF: 0.0207 AC: 926 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0206 AC: 539 AN: 26136

East Asian (EAS) AF: 0.00184 AC: 73 AN: 39700

South Asian (SAS) AF: 0.0927 AC: 7992 AN: 86242

European-Finnish (FIN) AF: 0.0243 AC: 1298 AN: 53414

Middle Eastern (MID) AF: 0.0626 AC: 361 AN: 5768

European-Non Finnish (NFE) AF: 0.0337 AC: 37506 AN: 1111978

Other (OTH) AF: 0.0407 AC: 2456 AN: 60396

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

African (AFR) AF: 0.0620 AC: 2578 AN: 41566

American (AMR) AF: 0.0288 AC: 441 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5182

South Asian (SAS) AF: 0.0938 AC: 453 AN: 4828

European-Finnish (FIN) AF: 0.0242 AC: 257 AN: 10620

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2172 AN: 68032

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0342 Hom.: 55

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
PhyloP100		2.5
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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