Variant 14-45096205-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017922.4(PRPF39):c.427G>A(p.Asp143Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000358 in 1,590,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

PRPF39
NM_017922.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

PRPF39 (HGNC:20314): (pre-mRNA processing factor 39) Predicted to be involved in mRNA 5'-splice site recognition. Predicted to be part of U1 snRNP; U2-type prespliceosome; and commitment complex. [provided by Alliance of Genome Resources, Apr 2022]

PRPF39 links:

PRPF39 (HGNC:):

PRPF39 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052084744).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF39	NM_017922.4 linkuse as main transcript	c.427G>A	p.Asp143Asn	missense_variant	3/14	ENST00000355765.11	NP_060392.3	Q86UA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF39	ENST00000355765.11 linkuse as main transcript	c.427G>A	p.Asp143Asn	missense_variant	3/14	1	NM_017922.4	ENSP00000348010.6		Q86UA1-1

Frequencies

GnomAD3 genomes

AF:

0.0000596

AC:

AN:

151052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000417

AC:

AN:

215796

Hom.:

AF XY:

0.0000432

AC XY:

AN XY:

115674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000737

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.0000333

AC:

AN:

1439326

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

713560

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000480

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000364

Gnomad4 OTH exome

AF:

0.0000671

GnomAD4 genome

AF:

0.0000595

AC:

AN:

151164

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73770

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000486

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.427G>A (p.D143N) alteration is located in exon 3 (coding exon 2) of the PRPF39 gene. This alteration results from a G to A substitution at nucleotide position 427, causing the aspartic acid (D) at amino acid position 143 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.63

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.0037

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.0046

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.17

N;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.94

N;N

REVEL

Benign

0.053

Sift

Benign

0.19

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.0090

B;.

Vest4

0.18

MVP

0.47

MPC

0.45

ClinPred

0.070

GERP RS

5.9

Varity_R

0.073

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over