rs34347250

Variant names:

• chr14-33950541-C-G
• NM_022073.4:c.212G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-33950541-C-G
• chr14-33950541-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: EGLN3 NM_022073.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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	c.212G>C	p.Arg71Pro	missense_variant	Exon 1 of 5	ENST00000250457.9	NP_071356.1
EGLN3	NM_001308103.2	c.75+137G>C		intron_variant	Intron 1 of 4		NP_001295032.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460350 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726342

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 Cov.: 32

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	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.80	D;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.74	T
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	D
GERP RS		5.7
Varity_R		0.70
gMVP		0.91

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: chr14-34419747;