17-50540468-G-C

Variant names:

• chr17-50540468-G-C
• rs2306002
• NM_017957.3:c.979+134G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017957.3(EPN3):​c.979+134G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPN3 NM_017957.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPN3	NM_017957.3	c.979+134G>C		intron_variant	Intron 6 of 9	ENST00000268933.8	NP_060427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPN3	ENST00000268933.8	c.979+134G>C		intron_variant	Intron 6 of 9	2	NM_017957.3	ENSP00000268933.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 656194 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 335968

African (AFR) AF: 0.00 AC: 0 AN: 16362

American (AMR) AF: 0.00 AC: 0 AN: 22080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15370

East Asian (EAS) AF: 0.00 AC: 0 AN: 31906

South Asian (SAS) AF: 0.00 AC: 0 AN: 52386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 451490

Other (OTH) AF: 0.00 AC: 0 AN: 32996

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.70
DANN	Benign	0.36
PhyloP100		-0.78

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

Other links and lift over

dbSNP: rs2306002; hg19: chr17-48617829;