chr10-49736483-G-A

Variant names:

• chr10-49736483-G-A
• rs12357255
• NM_018245.3:c.2628C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_018245.3(OGDHL):​c.2628C>T​(p.Ala876Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,613,706 control chromosomes in the GnomAD database, including 1,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.028 (93 hom., cov: 33)
  • Exomes 𝑓: 0.037 (1190 hom.)
• Consequence: OGDHL NM_018245.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.80
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-49736483-G-A is Benign according to our data. Variant chr10-49736483-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056267.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.8 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

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.2628C>T	p.Ala876Ala	synonymous	Exon 21 of 23	NP_060715.2	Q9ULD0-1
	OGDHL	NM_001347819.1		c.2628C>T	p.Ala876Ala	synonymous	Exon 21 of 23	NP_001334748.1	Q9ULD0-1
	OGDHL	NM_001143996.2		c.2457C>T	p.Ala819Ala	synonymous	Exon 20 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.2628C>T	p.Ala876Ala	synonymous	Exon 21 of 23	ENSP00000363216.4	Q9ULD0-1
	OGDHL	ENST00000852721.1		c.2721C>T	p.Ala907Ala	synonymous	Exon 22 of 24	ENSP00000522780.1
	OGDHL	ENST00000852716.1		c.2646C>T	p.Ala882Ala	synonymous	Exon 21 of 23	ENSP00000522775.1

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4204 AN: 152130 Hom.: 93 Cov.: 33

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0403

Gnomad OTH AF: 0.0340

GnomAD2 exomes AF: 0.0306 AC: 7670 AN: 250264 AF XY: 0.0315

Gnomad AFR exome AF: 0.00630

Gnomad AMR exome AF: 0.0205

Gnomad ASJ exome AF: 0.0917

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0142

Gnomad NFE exome AF: 0.0401

Gnomad OTH exome AF: 0.0356

GnomAD4 exome AF: 0.0369 AC: 53955 AN: 1461458 Hom.: 1190 Cov.: 35 AF XY: 0.0371 AC XY: 26948 AN XY: 727050

African (AFR) AF: 0.00747 AC: 250 AN: 33480

American (AMR) AF: 0.0220 AC: 985 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 2363 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0293 AC: 2530 AN: 86256

European-Finnish (FIN) AF: 0.0153 AC: 809 AN: 53046

Middle Eastern (MID) AF: 0.0685 AC: 395 AN: 5768

European-Non Finnish (NFE) AF: 0.0399 AC: 44411 AN: 1111978

Other (OTH) AF: 0.0366 AC: 2208 AN: 60380

GnomAD4 genome AF: 0.0276 AC: 4202 AN: 152248 Hom.: 93 Cov.: 33 AF XY: 0.0264 AC XY: 1964 AN XY: 74446

African (AFR) AF: 0.00700 AC: 291 AN: 41546

American (AMR) AF: 0.0301 AC: 461 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 307 AN: 3472

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5160

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4824

European-Finnish (FIN) AF: 0.0109 AC: 116 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0403 AC: 2739 AN: 68018

Other (OTH) AF: 0.0336 AC: 71 AN: 2112

Alfa AF: 0.0389 Hom.: 66

Bravo AF: 0.0279

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.0441

EpiControl AF: 0.0452

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	OGDHL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.038
DANN	Benign	0.43
PhyloP100		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	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: rs12357255; hg19: chr10-50944529; COSMIC: COSV65103265;