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GeneBe

14-33929099-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.11 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EGLN3NM_022073.4 linkuse as main transcriptc.591A>G p.Glu197= synonymous_variant 3/5 ENST00000250457.9
EGLN3NM_001308103.2 linkuse as main transcriptc.309A>G p.Glu103= synonymous_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EGLN3ENST00000250457.9 linkuse as main transcriptc.591A>G p.Glu197= synonymous_variant 3/51 NM_022073.4 P1
EGLN3ENST00000553215.5 linkuse as main transcriptc.309A>G p.Glu103= synonymous_variant 3/51
EGLN3ENST00000487915.6 linkuse as main transcriptc.237A>G p.Glu79= synonymous_variant 6/65
EGLN3ENST00000556785.1 linkuse as main transcriptn.355A>G non_coding_transcript_exon_variant 2/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00821
AC:
1250
AN:
152188
Hom.:
6
Cov.:
33
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.:
10
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.:
99
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00821
AC:
1250
AN:
152306
Hom.:
6
Cov.:
33
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.:
5
Bravo
AF:
0.00652
Asia WGS
AF:
0.00375
AC:
14
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs45570637; hg19: chr14-34398305; API