rs6998

Variant names:

• chr19-50860405-G-A
• rs6998
• NM_001648.2:c.*278G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-50860405-G-A
• chr19-50860405-G-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.*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
• Publications: 16 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 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.*278G>A		3_prime_UTR	Exon 5 of 5	NP_001639.1
	KLK3	NM_001030047.1		c.*789G>A		3_prime_UTR	Exon 5 of 5	NP_001025218.1
	KLK3	NM_001030048.1		c.*278G>A		3_prime_UTR	Exon 5 of 5	NP_001025219.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000326003.7	TSL:1 MANE Select	c.*278G>A		3_prime_UTR	Exon 5 of 5	ENSP00000314151.1
	KLK3	ENST00000360617.7	TSL:1	c.*789G>A		3_prime_UTR	Exon 5 of 5	ENSP00000353829.2
	KLK3	ENST00000422986.6	TSL:1	n.*720G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000393628.2

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

African (AFR) AF: 0.115 AC: 613 AN: 5326

American (AMR) AF: 0.392 AC: 2324 AN: 5922

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 1175 AN: 5134

East Asian (EAS) AF: 0.427 AC: 4399 AN: 10306

South Asian (SAS) AF: 0.165 AC: 1386 AN: 8384

European-Finnish (FIN) AF: 0.450 AC: 4077 AN: 9066

Middle Eastern (MID) AF: 0.173 AC: 123 AN: 710

European-Non Finnish (NFE) AF: 0.322 AC: 28786 AN: 89522

Other (OTH) AF: 0.296 AC: 2716 AN: 9190

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

African (AFR) AF: 0.129 AC: 5335 AN: 41460

American (AMR) AF: 0.378 AC: 5780 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3464

East Asian (EAS) AF: 0.430 AC: 2222 AN: 5168

South Asian (SAS) AF: 0.184 AC: 884 AN: 4808

European-Finnish (FIN) AF: 0.459 AC: 4844 AN: 10550

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22825 AN: 67928

Other (OTH) AF: 0.278 AC: 587 AN: 2110

Alfa AF: 0.310 Hom.: 12425

Bravo AF: 0.274

Asia WGS AF: 0.309 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.55
PhyloP100		-0.71
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: rs6998; hg19: chr19-51363661;