chr17-50543156-G-A

Position:

• chr17-50543156-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017957.3(EPN3):​c.*999G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,344 control chromosomes in the GnomAD database, including 1,568 homozygotes. 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: 𝑓 0.13 (1565 hom., cov: 33)
  • Exomes 𝑓: 0.23 (3 hom.)
• Consequence: EPN3 NM_017957.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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]

SPATA20 (HGNC:26125): (spermatogenesis associated 20) Predicted to be involved in carbohydrate metabolic process; cell differentiation; and spermatogenesis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPN3	NM_017957.3	c.*999G>A		3_prime_UTR_variant	10/10	ENST00000268933.8	NP_060427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPN3	ENST00000268933.8	c.*999G>A		3_prime_UTR_variant	10/10	2	NM_017957.3	ENSP00000268933	P1
SPATA20	ENST00000504334.5	c.-697G>A		5_prime_UTR_variant, NMD_transcript_variant	1/18	2		ENSP00000424215

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19653 AN: 152178 Hom.: 1564 Cov.: 33

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.229 AC: 11 AN: 48 Hom.: 3 Cov.: 0 AF XY: 0.133 AC XY: 4 AN XY: 30

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.129 AC: 19648 AN: 152296 Hom.: 1565 Cov.: 33 AF XY: 0.123 AC XY: 9138 AN XY: 74466

Gnomad4 AFR AF: 0.0572

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0905

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.160

Alfa AF: 0.170 Hom.: 3215

Bravo AF: 0.128

Asia WGS AF: 0.0420 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.83

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

LitVar

Other links and lift over

dbSNP: rs4793661; hg19: chr17-48620517;