rs1045531

chr8-142682129-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005672.5(PSCA):c.342C>A(p.Leu114=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,597,802 control chromosomes in the GnomAD database, including 163,485 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (14987 hom., cov: 34)
  • Exomes 𝑓: 0.45 (148498 hom.)
• Consequence: PSCA NM_005672.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-1.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSCA	NM_005672.5	c.342C>A	p.Leu114=	synonymous_variant	3/3	ENST00000301258.5
PSCA	NR_033343.2	n.589C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSCA	ENST00000301258.5	c.342C>A	p.Leu114=	synonymous_variant	3/3	1	NM_005672.5	P1
PSCA	ENST00000510969.1	n.565C>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67115 AN: 151980 Hom.: 14960 Cov.: 34

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.442

GnomAD3 exomes AF: 0.454 AC: 103821 AN: 228692 Hom.: 23928 AF XY: 0.452 AC XY: 57081 AN XY: 126308

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.505

Gnomad EAS exome AF: 0.312

Gnomad SAS exome AF: 0.441

Gnomad FIN exome AF: 0.497

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.451 AC: 651339 AN: 1445702 Hom.: 148498 Cov.: 60 AF XY: 0.451 AC XY: 324320 AN XY: 719518

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.558

Gnomad4 ASJ exome AF: 0.506

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.442 AC: 67181 AN: 152100 Hom.: 14987 Cov.: 34 AF XY: 0.442 AC XY: 32897 AN XY: 74360

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.444

Alfa AF: 0.456 Hom.: 5660

Bravo AF: 0.439

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.38
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1045531; hg19: chr8-143763547; COSMIC: COSV56652582; COSMIC: COSV56652582;