Variant 14-33929099-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_022073.4(EGLN3):c.591A>G(p.Glu197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,614,086 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 99 hom. )

Consequence

EGLN3
NM_022073.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

EGLN3 (HGNC:14661): (egl-9 family hypoxia inducible factor 3) Enables peptidyl-proline 4-dioxygenase activity. Involved in several processes, including activation of cysteine-type endopeptidase activity involved in apoptotic process; peptidyl-proline hydroxylation to 4-hydroxy-L-proline; and response to hypoxia. Located in cytosol and nucleus. Implicated in renal cell carcinoma. Biomarker of clear cell renal cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

EGLN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 14-33929099-T-C is Benign according to our data. Variant chr14-33929099-T-C is described in ClinVar as [Benign]. Clinvar id is 783045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.11 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGLN3	NM_022073.4 linkuse as main transcript	c.591A>G	p.Glu197=	synonymous_variant	3/5	ENST00000250457.9	NP_071356.1
EGLN3	NM_001308103.2 linkuse as main transcript	c.309A>G	p.Glu103=	synonymous_variant	3/5		NP_001295032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
EGLN3	ENST00000250457.9 linkuse as main transcript	c.591A>G	p.Glu197=	synonymous_variant	3/5	1	NM_022073.4	ENSP00000250457	P1
EGLN3	ENST00000553215.5 linkuse as main transcript	c.309A>G	p.Glu103=	synonymous_variant	3/5	1		ENSP00000447470
EGLN3	ENST00000487915.6 linkuse as main transcript	c.237A>G	p.Glu79=	synonymous_variant	6/6	5		ENSP00000451316
EGLN3	ENST00000556785.1 linkuse as main transcript	n.355A>G		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.00821

AC:

1250

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00926

AC:

2327

AN:

251350

Hom.:

AF XY:

0.00976

AC XY:

1326

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00903

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.0159

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00994

GnomAD4 exome

AF:

0.00937

AC:

13695

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00972

AC XY:

7066

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00420

Gnomad4 ASJ exome

AF:

0.0105

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.0160

Gnomad4 NFE exome

AF:

0.00971

Gnomad4 OTH exome

AF:

0.00795

GnomAD4 genome

AF:

0.00821

AC:

1250

AN:

152306

Hom.:

Cov.:

AF XY:

0.00858

AC XY:

639

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00457

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00938

Hom.:

Bravo

AF:

0.00652

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.6

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over