rs3736001

Variant names:

• chr8-142681389-G-A
• rs3736001
• NM_005672.5:c.88G>A

Your query was ambiguous. Multiple possible variants found:

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

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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 20 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005672.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSCA	NM_005672.5	MANE Select	c.88G>A	p.Glu30Lys	missense	Exon 2 of 3	NP_005663.2
	PSCA	NR_033343.2		n.335G>A		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSCA	ENST00000301258.5	TSL:1 MANE Select	c.88G>A	p.Glu30Lys	missense	Exon 2 of 3	ENSP00000301258.4
	PSCA	ENST00000918921.1		c.88G>A	p.Glu30Lys	missense	Exon 3 of 4	ENSP00000588980.1
	PSCA	ENST00000966863.1		c.88G>A	p.Glu30Lys	missense	Exon 2 of 3	ENSP00000636922.1

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

GnomAD2 exomes AF: 0.0233 AC: 5002 AN: 214314 AF XY: 0.0250

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.: 32 AF XY: 0.0213 AC XY: 15254 AN XY: 714500

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: 89 AN: 5736

European-Non Finnish (NFE) AF: 0.0163 AC: 17956 AN: 1102078

Other (OTH) AF: 0.0251 AC: 1499 AN: 59662

GnomAD4 genome AF: 0.0156 AC: 2371 AN: 152284 Hom.: 59 Cov.: 33 AF XY: 0.0164 AC XY: 1220 AN XY: 74454

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: 20 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: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1060 AN: 68016

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.0157 Hom.: 117

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 v4.9

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
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.96
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.016
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.088
MPC		0.017
ClinPred		0.0012	T
GERP RS		-0.13
Varity_R		0.047
gMVP		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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