rs119476044

Variant names:

• chr1-231370598-C-G
• NM_022051.3:c.1112G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-231370598-C-G
• chr1-231370598-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM5 PP3_Moderate

The NM_022051.3(EGLN1):​c.1112G>C​(p.Arg371Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R371H) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EGLN1 NM_022051.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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]

ENSG00000287856 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-231370598-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 4356.Status of the report is no_assertion_criteria_provided, 0 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN1	NM_022051.3	c.1112G>C	p.Arg371Pro	missense_variant	Exon 3 of 5	ENST00000366641.4	NP_071334.1
EGLN1	NM_001377260.1	c.1112G>C	p.Arg371Pro	missense_variant	Exon 3 of 4		NP_001364189.1
EGLN1	NM_001377261.1	c.1012-2962G>C		intron_variant	Intron 2 of 3		NP_001364190.1
EGLN1	XM_024447734.2	c.1012-2962G>C		intron_variant	Intron 2 of 2		XP_024303502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN1	ENST00000366641.4	c.1112G>C	p.Arg371Pro	missense_variant	Exon 3 of 5	1	NM_022051.3	ENSP00000355601.3
ENSG00000287856	ENST00000662216.1	c.251G>C	p.Arg84Pro	missense_variant	Exon 5 of 7			ENSP00000499467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Pathogenic	3.9	H
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.93
MutPred		0.68		Loss of stability (P = 0.0225);
MVP		0.85
MPC		2.6
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.97
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-231506344;