Variant 1-231421530-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022051.3(EGLN1):c.359C>A(p.Pro120Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. P120L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EGLN1
NM_022051.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.433

Variant links:

Genes affected

EGLN1 (HGNC:1232): (egl-9 family hypoxia inducible factor 1) The protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Mutations in this gene are associated with erythrocytosis familial type 3 (ECYT3). [provided by RefSeq, Nov 2009]

EGLN1 links:

ENSG00000287856 (HGNC:):

ENSG00000287856 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22419116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGLN1	NM_022051.3 linkuse as main transcript	c.359C>A	p.Pro120Gln	missense_variant	1/5	ENST00000366641.4	NP_071334.1	Q9GZT9-1R4SCQ0
EGLN1	NM_001377260.1 linkuse as main transcript	c.359C>A	p.Pro120Gln	missense_variant	1/4		NP_001364189.1
EGLN1	NM_001377261.1 linkuse as main transcript	c.359C>A	p.Pro120Gln	missense_variant	1/4		NP_001364190.1
EGLN1	XM_024447734.2 linkuse as main transcript	c.359C>A	p.Pro120Gln	missense_variant	1/3		XP_024303502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EGLN1	ENST00000366641.4 linkuse as main transcript	c.359C>A	p.Pro120Gln	missense_variant	1/5	1	NM_022051.3	ENSP00000355601.3	Q9GZT9-1
ENSG00000287856	ENST00000662216.1 linkuse as main transcript	c.30+40908C>A		intron_variant				ENSP00000499467.1	A0A590UJK7
ENSG00000287856	ENST00000653908.1 linkuse as main transcript	c.30+40908C>A		intron_variant				ENSP00000499669.1	A0A590UK27
ENSG00000287856	ENST00000653198.1 linkuse as main transcript	n.433+40942C>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151672

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1148600

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

549254

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74072

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.25

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.55

MutationAssessor

Benign

0.90

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.59

REVEL

Benign

0.22

Sift

Benign

0.35

Sift4G

Benign

0.47

Polyphen

0.84

Vest4

0.11

MutPred

0.21

Loss of loop (P = 0.0022);

MVP

0.61

MPC

2.0

ClinPred

0.29

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.38

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over