NM_022051.3:c.405C>G

Variant names:

• chr1-231421484-G-C
• NM_022051.3:c.405C>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_022051.3(EGLN1):​c.405C>G​(p.Gly135Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000828 in 1,207,432 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. Synonymous variant affecting the same amino acid position (i.e. G135G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: EGLN1 NM_022051.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=0.005 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN1	NM_022051.3	c.405C>G	p.Gly135Gly	synonymous_variant	Exon 1 of 5	ENST00000366641.4	NP_071334.1
EGLN1	NM_001377260.1	c.405C>G	p.Gly135Gly	synonymous_variant	Exon 1 of 4		NP_001364189.1
EGLN1	NM_001377261.1	c.405C>G	p.Gly135Gly	synonymous_variant	Exon 1 of 4		NP_001364190.1
EGLN1	XM_024447734.2	c.405C>G	p.Gly135Gly	synonymous_variant	Exon 1 of 3		XP_024303502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN1	ENST00000366641.4	c.405C>G	p.Gly135Gly	synonymous_variant	Exon 1 of 5	1	NM_022051.3	ENSP00000355601.3
ENSG00000287856	ENST00000662216.1	c.30+40954C>G		intron_variant	Intron 3 of 6			ENSP00000499467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.28e-7 AC: 1 AN: 1207432 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 582276

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: 0.00000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.56

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: chr1-231557230;