10-49734717-C-T

Variant names:

• chr10-49734717-C-T
• rs6816
• NM_018245.3:c.*511G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018245.3(OGDHL):​c.*511G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,254 control chromosomes in the GnomAD database, including 13,647 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 0.38 (13628 hom., cov: 33)
  • Exomes 𝑓: 0.46 (19 hom.)
• Consequence: OGDHL NM_018245.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGDHL	NM_018245.3	c.*511G>A		3_prime_UTR_variant	Exon 23 of 23	ENST00000374103.9	NP_060715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGDHL	ENST00000374103	c.*511G>A		3_prime_UTR_variant	Exon 23 of 23	1	NM_018245.3	ENSP00000363216.4
OGDHL	ENST00000419399	c.*511G>A		3_prime_UTR_variant	Exon 22 of 22	2		ENSP00000401356.1
OGDHL	ENST00000432695	c.*511G>A		3_prime_UTR_variant	Exon 21 of 21	2		ENSP00000390240.1
OGDHL	ENST00000490844.1	n.2580G>A		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58304 AN: 151972 Hom.: 13630 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.457 AC: 75 AN: 164 Hom.: 19 Cov.: 0 AF XY: 0.489 AC XY: 46 AN XY: 94

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.383 AC: 58309 AN: 152090 Hom.: 13628 Cov.: 33 AF XY: 0.388 AC XY: 28887 AN XY: 74360

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.404

Alfa AF: 0.432 Hom.: 19148

Bravo AF: 0.375

Asia WGS AF: 0.615 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.74

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: rs6816; hg19: chr10-50942763;