rs1053972

Variant names:

• chr19-50855373-C-T
• rs1053972
• NM_001648.2:c.46+372C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001648.2(KLK3):​c.46+372C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 258,464 control chromosomes in the GnomAD database, including 10,063 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 0.24 (5336 hom., cov: 31)
  • Exomes 𝑓: 0.28 (4727 hom.)
• Consequence: KLK3 NM_001648.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001648.2. 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
	KLK3	NM_001648.2	MANE Select	c.46+372C>T		intron	N/A	NP_001639.1	Q546G3
	KLK3	NM_001030047.1		c.46+372C>T		intron	N/A	NP_001025218.1	P07288-2
	KLK3	NM_001030048.1		c.46+372C>T		intron	N/A	NP_001025219.1	P07288-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000326003.7	TSL:1 MANE Select	c.46+372C>T		intron	N/A	ENSP00000314151.1	P07288-1
	KLK3	ENST00000360617.7	TSL:1	c.46+372C>T		intron	N/A	ENSP00000353829.2	P07288-2
	KLK3	ENST00000593997.5	TSL:1	c.46+372C>T		intron	N/A	ENSP00000472907.1	P07288-5

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36581 AN: 151886 Hom.: 5329 Cov.: 31

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.276 AC: 29341 AN: 106460 Hom.: 4727 Cov.: 0 AF XY: 0.270 AC XY: 14940 AN XY: 55388

African (AFR) AF: 0.0813 AC: 280 AN: 3444

American (AMR) AF: 0.374 AC: 2001 AN: 5354

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 767 AN: 3324

East Asian (EAS) AF: 0.454 AC: 2821 AN: 6220

South Asian (SAS) AF: 0.175 AC: 1882 AN: 10770

European-Finnish (FIN) AF: 0.376 AC: 1876 AN: 4994

Middle Eastern (MID) AF: 0.131 AC: 64 AN: 488

European-Non Finnish (NFE) AF: 0.275 AC: 18005 AN: 65568

Other (OTH) AF: 0.261 AC: 1645 AN: 6298

GnomAD4 genome AF: 0.241 AC: 36602 AN: 152004 Hom.: 5336 Cov.: 31 AF XY: 0.245 AC XY: 18170 AN XY: 74306

African (AFR) AF: 0.0905 AC: 3753 AN: 41480

American (AMR) AF: 0.331 AC: 5060 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3472

East Asian (EAS) AF: 0.433 AC: 2233 AN: 5154

South Asian (SAS) AF: 0.171 AC: 825 AN: 4822

European-Finnish (FIN) AF: 0.382 AC: 4029 AN: 10554

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19122 AN: 67938

Other (OTH) AF: 0.232 AC: 488 AN: 2104

Alfa AF: 0.266 Hom.: 1490

Bravo AF: 0.232

Asia WGS AF: 0.295 AC: 1025 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.53
PhyloP100		-1.6
PromoterAI		-0.0012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1053972; hg19: chr19-51358629;