dbSNP rs3736001: PSCA:p.Glu30Lys (chr8-142681389-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

20 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PSCA	NM_005672.5 link	c.88G>A	p.Glu30Lys	missense_variant	Exon 2 of 3	ENST00000301258.5	NP_005663.2	O43653D3DWI6
PSCA	NR_033343.2 link	n.335G>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000301258.5 link	c.88G>A	p.Glu30Lys	missense_variant	Exon 2 of 3	1	NM_005672.5	ENSP00000301258.4		O43653

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

GnomAD2 exomes

AF:

0.0233

AC:

5002

AN:

214314

AF XY:

0.0250

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 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

African (AFR)

AF:

0.00318

AC:

105

AN:

33000

American (AMR)

AF:

0.00678

AC:

285

AN:

42012

Ashkenazi Jewish (ASJ)

AF:

0.00693

AC:

178

AN:

25688

East Asian (EAS)

AF:

0.109

AC:

4191

AN:

38626

South Asian (SAS)

AF:

0.0528

AC:

4359

AN:

82534

European-Finnish (FIN)

AF:

0.0104

AC:

533

AN:

51468

Middle Eastern (MID)

AF:

0.0155

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0163

AC:

17956

AN:

1102078

Other (OTH)

AF:

0.0251

AC:

1499

AN:

59662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1514

3028

4542

6056

7570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

776

1552

2328

3104

3880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0156

AC:

2371

AN:

152284

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1220

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00450

AC:

187

AN:

41556

American (AMR)

AF:

0.0100

AC:

153

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.106

AC:

548

AN:

5168

South Asian (SAS)

AF:

0.0475

AC:

229

AN:

4826

European-Finnish (FIN)

AF:

0.0120

AC:

127

AN:

10622

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0156

AC:

1060

AN:

68016

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

120

240

361

481

601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0157

Hom.:

117

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

(source)

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

PhyloP100

-0.96

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over