rs1258184

Variant names:

• chr10-49752163-G-A
• rs1258184
• NM_018245.3:c.564C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-49752163-G-A
• chr10-49752163-G-C

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.564C>T​(p.Leu188Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,613,382 control chromosomes in the GnomAD database, including 193,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.41 (14875 hom., cov: 32)
  • Exomes 𝑓: 0.48 (178488 hom.)
• Consequence: OGDHL NM_018245.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.99
• Publications: 17 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=-0.7).
• BP6: Variant 10-49752163-G-A is Benign according to our data. Variant chr10-49752163-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059593.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGDHL	NM_018245.3	c.564C>T	p.Leu188Leu	synonymous_variant	Exon 5 of 23	ENST00000374103.9	NP_060715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGDHL	ENST00000374103.9	c.564C>T	p.Leu188Leu	synonymous_variant	Exon 5 of 23	1	NM_018245.3	ENSP00000363216.4
OGDHL	ENST00000419399.4	c.393C>T	p.Leu131Leu	synonymous_variant	Exon 4 of 22	2		ENSP00000401356.1
OGDHL	ENST00000432695.2	c.-64C>T		5_prime_UTR_variant	Exon 3 of 21	2		ENSP00000390240.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62596 AN: 151936 Hom.: 14876 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.422

GnomAD2 exomes AF: 0.489 AC: 122670 AN: 251048 AF XY: 0.483

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.548

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.891

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.481

Gnomad OTH exome AF: 0.463

GnomAD4 exome AF: 0.485 AC: 708694 AN: 1461328 Hom.: 178488 Cov.: 47 AF XY: 0.481 AC XY: 350030 AN XY: 726986

African (AFR) AF: 0.173 AC: 5777 AN: 33476

American (AMR) AF: 0.541 AC: 24186 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 8673 AN: 26128

East Asian (EAS) AF: 0.885 AC: 35148 AN: 39698

South Asian (SAS) AF: 0.411 AC: 35446 AN: 86248

European-Finnish (FIN) AF: 0.513 AC: 27400 AN: 53368

Middle Eastern (MID) AF: 0.383 AC: 2211 AN: 5768

European-Non Finnish (NFE) AF: 0.487 AC: 541531 AN: 1111598

Other (OTH) AF: 0.469 AC: 28322 AN: 60372

GnomAD4 genome AF: 0.412 AC: 62608 AN: 152054 Hom.: 14875 Cov.: 32 AF XY: 0.415 AC XY: 30858 AN XY: 74330

African (AFR) AF: 0.188 AC: 7813 AN: 41512

American (AMR) AF: 0.486 AC: 7432 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3470

East Asian (EAS) AF: 0.888 AC: 4565 AN: 5140

South Asian (SAS) AF: 0.427 AC: 2051 AN: 4806

European-Finnish (FIN) AF: 0.510 AC: 5388 AN: 10574

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32670 AN: 67944

Other (OTH) AF: 0.426 AC: 900 AN: 2114

Alfa AF: 0.444 Hom.: 23344

Bravo AF: 0.405

Asia WGS AF: 0.640 AC: 2224 AN: 3478

EpiCase AF: 0.467

EpiControl AF: 0.463

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

OGDHL-related disorder Benign:1

Nov 11, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.0
DANN	Benign	0.65
PhyloP100		-3.0
Mutation Taster		=298/2	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: rs1258184; hg19: chr10-50960209; COSMIC: COSV65103994; COSMIC: COSV65103994;