Genetic Variant EGLN3:p.Arg71Pro (chr14-33950541-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_022073.4(EGLN3):c.212G>C(p.Arg71Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

EGLN3
NM_022073.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00

Publications

0 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34749138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN3	NM_022073.4 link	c.212G>C	p.Arg71Pro	missense_variant	Exon 1 of 5	ENST00000250457.9	NP_071356.1	Q9H6Z9
EGLN3	NM_001308103.2 link	c.75+137G>C		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>C	p.Arg71Pro	missense_variant	Exon 1 of 5	1	NM_022073.4	ENSP00000250457.4	Q9H6Z9
EGLN3	ENST00000553215.5 link	c.75+137G>C		intron_variant	Intron 1 of 4	1		ENSP00000447470.1	F8W1G2
EGLN3	ENST00000547327.2 link	c.212G>C	p.Arg71Pro	missense_variant	Exon 1 of 1	6		ENSP00000446572.2	F8VR39
EGLN3	ENST00000487915.6 link	c.4-19326G>C		intron_variant	Intron 4 of 5	5		ENSP00000451316.1	G3V3M1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460350

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52842

Middle Eastern (MID)

AF:

0.000695

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111372

Other (OTH)

AF:

0.00

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.80

D;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

T;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.

PhyloP100

2.0

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0070

D;D

Sift4G

Benign

0.066

T;D

Polyphen

0.026

B;D

Vest4

0.56

MutPred

0.42

Loss of MoRF binding (P = 0.0149);Loss of MoRF binding (P = 0.0149);

MVP

0.71

MPC

1.5

ClinPred

0.94

GERP RS

5.7

PromoterAI

0.093

Neutral

(source)

Varity_R

0.70

gMVP

0.91

Mutation Taster

=58/42

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over