rs113014306

Variant names:

• chr10-49735330-C-T
• rs113014306
• NM_018245.3:c.2931G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-49735330-C-T
• chr10-49735330-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018245.3(OGDHL):​c.2931G>A​(p.Ala977Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,613,470 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00083 (23 hom.)
• Consequence: OGDHL NM_018245.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.78
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 10-49735330-C-T is Benign according to our data. Variant chr10-49735330-C-T is described in ClinVar as Benign. ClinVar VariationId is 719468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.78 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00805 (1226/152350) while in subpopulation AFR AF = 0.0271 (1127/41580). AF 95% confidence interval is 0.0258. There are 14 homozygotes in GnomAd4. There are 576 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018245.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGDHL	NM_018245.3	MANE Select	c.2931G>A	p.Ala977Ala	synonymous	Exon 23 of 23	NP_060715.2	Q9ULD0-1
	OGDHL	NM_001347819.1		c.2931G>A	p.Ala977Ala	synonymous	Exon 23 of 23	NP_001334748.1	Q9ULD0-1
	OGDHL	NM_001143996.2		c.2760G>A	p.Ala920Ala	synonymous	Exon 22 of 22	NP_001137468.1	Q9ULD0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGDHL	ENST00000374103.9	TSL:1 MANE Select	c.2931G>A	p.Ala977Ala	synonymous	Exon 23 of 23	ENSP00000363216.4	Q9ULD0-1
	OGDHL	ENST00000852721.1		c.3024G>A	p.Ala1008Ala	synonymous	Exon 24 of 24	ENSP00000522780.1
	OGDHL	ENST00000852716.1		c.2949G>A	p.Ala983Ala	synonymous	Exon 23 of 23	ENSP00000522775.1

Frequencies

GnomAD3 genomes AF: 0.00788 AC: 1200 AN: 152234 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00203 AC: 509 AN: 250754 AF XY: 0.00148

Gnomad AFR exome AF: 0.0281

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000984

GnomAD4 exome AF: 0.000832 AC: 1215 AN: 1461120 Hom.: 23 Cov.: 32 AF XY: 0.000700 AC XY: 509 AN XY: 726874

African (AFR) AF: 0.0282 AC: 944 AN: 33460

American (AMR) AF: 0.00172 AC: 77 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00112 AC: 6 AN: 5342

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111872

Other (OTH) AF: 0.00257 AC: 155 AN: 60346

GnomAD4 genome AF: 0.00805 AC: 1226 AN: 152350 Hom.: 14 Cov.: 33 AF XY: 0.00773 AC XY: 576 AN XY: 74502

African (AFR) AF: 0.0271 AC: 1127 AN: 41580

American (AMR) AF: 0.00549 AC: 84 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00292 Hom.: 2

Bravo AF: 0.00940

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.53
DANN	Benign	0.59
PhyloP100		-3.8
Mutation Taster		=98/2	polymorphism

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: rs113014306; hg19: chr10-50943376; COSMIC: COSV65102268;