Variant 8-142681389-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005672.5(PSCA):c.88G>A(p.Glu30Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,593,088 control chromosomes in the GnomAD database, including 712 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.016 ( 59 hom., cov: 33)

Exomes 𝑓: 0.020 ( 653 hom. )

Consequence

PSCA
NM_005672.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.962

Variant links:

Genes affected

PSCA (HGNC:9500): (prostate stem cell antigen) This gene encodes a glycosylphosphatidylinositol-anchored cell membrane glycoprotein. In addition to being highly expressed in the prostate it is also expressed in the bladder, placenta, colon, kidney, and stomach. This gene is up-regulated in a large proportion of prostate cancers and is also detected in cancers of the bladder and pancreas. This gene includes a polymorphism that results in an upstream start codon in some individuals; this polymorphism is thought to be associated with a risk for certain gastric and bladder cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

PSCA links:

JRK (HGNC:6199): (Jrk helix-turn-helix protein) This gene encodes a conserved protein that is similar to DNA-binding proteins, such as major centromere autoantigen B (CENPB). Inactivation of the related gene in mice resulted in epileptic seizures. Childhood Absence Epilepsy (CAE) has been mapped to the same chromosomal location (8q24.3) as this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

JRK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSCA	NM_005672.5 linkuse as main transcript	c.88G>A	p.Glu30Lys	missense_variant	2/3	ENST00000301258.5
PSCA	NR_033343.2 linkuse as main transcript	n.335G>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSCA	ENST00000301258.5 linkuse as main transcript	c.88G>A	p.Glu30Lys	missense_variant	2/3	1	NM_005672.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2368

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00451

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0474

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0233

AC:

5002

AN:

214314

Hom.:

161

AF XY:

0.0250

AC XY:

2906

AN XY:

116018

show subpopulations

Gnomad AFR exome

AF:

0.00423

Gnomad AMR exome

AF:

0.00660

Gnomad ASJ exome

AF:

0.00642

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.0517

Gnomad FIN exome

AF:

0.0127

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0233

GnomAD4 exome

AF:

0.0203

AC:

29195

AN:

1440804

Hom.:

653

Cov.:

AF XY:

0.0213

AC XY:

15254

AN XY:

714500

show subpopulations

Gnomad4 AFR exome

AF:

0.00318

Gnomad4 AMR exome

AF:

0.00678

Gnomad4 ASJ exome

AF:

0.00693

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.0528

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.0163

Gnomad4 OTH exome

AF:

0.0251

GnomAD4 genome

AF:

0.0156

AC:

2371

AN:

152284

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1220

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00450

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.0475

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.0156

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0141

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0176

AC:

ESP6500AA

AF:

0.00383

AC:

ESP6500EA

AF:

0.0142

AC:

120

ExAC

AF:

0.0209

AC:

2522

Asia WGS

AF:

0.0820

AC:

285

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.81

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.24

N;N

REVEL

Benign

0.016

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.088

MPC

0.017

ClinPred

0.0012

GERP RS

-0.13

Varity_R

0.047

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.35

Position offset: -4

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over