Genetic Variant NM_017957.3:c.*999G>A (chr17-50543156-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

6 publications found

Variant links:

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]

EPN3 links:

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]

SPATA20 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPN3	NM_017957.3 link	c.*999G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000268933.8	NP_060427.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
EPN3	ENST00000268933.8 link	c.*999G>A	3_prime_UTR_variant	Exon 10 of 10	2	NM_017957.3	ENSP00000268933.3
SPATA20	ENST00000504334.5 link	n.-697G>A	non_coding_transcript_exon_variant	Exon 1 of 18	2		ENSP00000424215.1
SPATA20	ENST00000504334.5 link	n.-697G>A	5_prime_UTR_variant	Exon 1 of 18	2		ENSP00000424215.1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19653

AN:

152178

Hom.:

1564

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.133

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.129

AC:

19648

AN:

152296

Hom.:

1565

Cov.:

AF XY:

0.123

AC XY:

9138

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0572

AC:

2376

AN:

41570

American (AMR)

AF:

0.125

AC:

1915

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

780

AN:

3470

East Asian (EAS)

AF:

0.00347

AC:

AN:

5186

South Asian (SAS)

AF:

0.0905

AC:

437

AN:

4828

European-Finnish (FIN)

AF:

0.107

AC:

1136

AN:

10610

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12402

AN:

68002

Other (OTH)

AF:

0.160

AC:

339

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

894

1788

2681

3575

4469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.167

Hom.:

3978

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

(source)

DANN

Benign

0.83

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over