rs6998

chr19-50860405-G-Achr19-50860405-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001648.2(KLK3):c.*278G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 295,536 control chromosomes in the GnomAD database, including 15,238 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 0.29 (7366 hom., cov: 32)
  • Exomes 𝑓: 0.32 (7872 hom.)
• Consequence: KLK3 NM_001648.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

Genes affected

KLK3 (HGNC:6364): (kallikrein related peptidase 3) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. The gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. It encodes a single-chain glycoprotein, a protease which is synthesized in the epithelial cells of the prostate gland, and is present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. The serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK3	NM_001648.2	c.*278G>A		3_prime_UTR_variant	5/5	ENST00000326003.7
KLK3	NM_001030047.1	c.*789G>A		3_prime_UTR_variant	5/5
KLK3	NM_001030048.1	c.*278G>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK3	ENST00000326003.7	c.*278G>A		3_prime_UTR_variant	5/5	1	NM_001648.2	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43614 AN: 151858 Hom.: 7362 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.318 AC: 45599 AN: 143560 Hom.: 7872 Cov.: 0 AF XY: 0.313 AC XY: 23124 AN XY: 73856

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.287 AC: 43634 AN: 151976 Hom.: 7366 Cov.: 32 AF XY: 0.291 AC XY: 21582 AN XY: 74288

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.278

Alfa AF: 0.312 Hom.: 8634

Bravo AF: 0.274

Asia WGS AF: 0.309 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.30
Dann	Benign	0.55

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: rs6998; hg19: chr19-51363661;