14-33950541-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_022073.4(EGLN3):c.212G>A(p.Arg71Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000709 in 1,612,628 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

EGLN3
NM_022073.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.00

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055088103).

BP6

Variant 14-33950541-C-T is Benign according to our data. Variant chr14-33950541-C-T is described in ClinVar as [Benign]. Clinvar id is 715664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN3	NM_022073.4 link	c.212G>A	p.Arg71Gln	missense_variant	Exon 1 of 5	ENST00000250457.9	NP_071356.1	Q9H6Z9
EGLN3	NM_001308103.2 link	c.75+137G>A		intron_variant	Intron 1 of 4		NP_001295032.1	Q9H6Z9Q3T1B0F8W1G2B3KVT0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EGLN3	ENST00000250457.9 link	c.212G>A	p.Arg71Gln	missense_variant	Exon 1 of 5	1	NM_022073.4	ENSP00000250457.4	Q9H6Z9
EGLN3	ENST00000553215.5 link	c.75+137G>A		intron_variant	Intron 1 of 4	1		ENSP00000447470.1	F8W1G2
EGLN3	ENST00000547327.2 link	c.212G>A	p.Arg71Gln	missense_variant	Exon 1 of 1	6		ENSP00000446572.2	F8VR39
EGLN3	ENST00000487915.6 link	c.4-19326G>A		intron_variant	Intron 4 of 5	5		ENSP00000451316.1	G3V3M1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

529

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

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:

0.00335

GnomAD2 exomes

AF:

0.000882

AC:

216

AN:

244984

AF XY:

0.000711

show subpopulations

Gnomad AFR exome

AF:

0.0112

Gnomad AMR exome

AF:

0.000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000560

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000729

Gnomad OTH exome

AF:

0.000997

GnomAD4 exome

AF:

0.000418

AC:

611

AN:

1460350

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

268

AN XY:

726342

show subpopulations

African (AFR)

AF:

0.0133

AC:

446

AN:

33442

American (AMR)

AF:

0.00103

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52842

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000504

AC:

AN:

1111372

Other (OTH)

AF:

0.000829

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00349

AC:

532

AN:

152278

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

252

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0118

AC:

489

AN:

41568

American (AMR)

AF:

0.00209

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68010

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00397

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00110

AC:

133

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PhyloP100

2.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.062

Sift

Benign

0.36

T;T

Sift4G

Benign

0.22

T;D

Polyphen

0.24

B;D

Vest4

0.12

MVP

0.65

MPC

1.2

ClinPred

0.018

GERP RS

5.7

PromoterAI

-0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.66

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over