dbSNP rs1045531: PSCA:p.Leu114Leu (chr8-142682129-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005672.5(PSCA):c.342C>A(p.Leu114Leu) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

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 made for transcript

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 rank	MANE	Protein	UniProt
PSCA	NM_005672.5 link	c.342C>A	p.Leu114Leu	synonymous_variant	Exon 3 of 3	ENST00000301258.5	NP_005663.2	O43653D3DWI6
PSCA	NR_033343.2 link	n.589C>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000301258.5 link	c.342C>A	p.Leu114Leu	synonymous_variant	Exon 3 of 3	1	NM_005672.5	ENSP00000301258.4		O43653

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67115

AN:

151980

Hom.:

14960

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.451

AC XY:

324320

AN XY:

719518

show subpopulations

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.:

AF XY:

0.442

AC XY:

32897

AN XY:

74360

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over