rs3785915

Positions:

• chr17-50536476-A-C
• chr17-50536476-A-G
• chr17-50536476-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017957.3(EPN3):​c.-81A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,796 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: 30)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: EPN3 NM_017957.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59

Genes affected

EPN3 (HGNC:18235): (epsin 3) Predicted to enable clathrin binding activity and phospholipid binding activity. Predicted to be involved in endocytosis. Located in clathrin-coated vesicle; nucleoplasm; and perinuclear region of cytoplasm. Is extrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPN3	NM_017957.3	c.-81A>C		5_prime_UTR_variant	2/10	ENST00000268933.8	NP_060427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPN3	ENST00000268933.8	c.-81A>C		5_prime_UTR_variant	2/10	2	NM_017957.3	ENSP00000268933	P1
	ENST00000654456.1	n.482+1451T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436796 Hom.: 0 Cov.: 66 AF XY: 0.00000140 AC XY: 1 AN XY: 715284

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3785915; hg19: chr17-48613837;