rs3736001

Positions:

• chr8-142681389-G-A
• chr8-142681389-G-T

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962

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]

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]

ACMG classification

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	c.88G>A	p.Glu30Lys	missense_variant	2/3	ENST00000301258.5
PSCA	NR_033343.2	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	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.: 59 Cov.: 33

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

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

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

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
MutationTaster	Benign	1.0	P;P
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

Other links and lift over

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