rs3736001

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

16

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]

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 Protein UniProt
PSCANM_005672.5 linkuse as main transcriptc.88G>A p.Glu30Lys missense_variant 2/3 ENST00000301258.5 NP_005663.2 O43653D3DWI6
PSCANR_033343.2 linkuse as main transcriptn.335G>A non_coding_transcript_exon_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSCAENST00000301258.5 linkuse as main transcriptc.88G>A p.Glu30Lys missense_variant 2/31 NM_005672.5 ENSP00000301258.4 O43653

Frequencies

GnomAD3 genomes
AF:
0.0156
AC:
2368
AN:
152164
Hom.:
59
Cov.:
33
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.:
32
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.:
59
Cov.:
33
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.:
78
Bravo
AF:
0.0141
TwinsUK
AF:
0.0148
AC:
55
ALSPAC
AF:
0.0176
AC:
68
ESP6500AA
AF:
0.00383
AC:
16
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
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
12
DANN
Benign
0.81
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.49
T;T
MetaRNN
Benign
0.0018
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.31
T
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
T
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.

Other links and lift over

dbSNP: rs3736001; hg19: chr8-143762807; COSMIC: COSV56653753; API