rs3865443

Positions:

• chr19-51034426-C-A
• chr19-51034426-C-G
• chr19-51034426-C-T

Variant summary

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

The NM_001370125.1(KLK12):​c.37+159G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,477,384 control chromosomes in the GnomAD database, including 49,775 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 0.26 (5425 hom., cov: 32)
  • Exomes 𝑓: 0.25 (44350 hom.)
• Consequence: KLK12 NM_001370125.1 intron
• Scores: Splicing: ADA: 0.00003319
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

Genes affected

KLK12 (HGNC:6360): (kallikrein related peptidase 12) 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. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternate splicing of this gene results in three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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 = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK12	NM_001370125.1	c.37+159G>T		intron_variant		ENST00000684732.1	NP_001357054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK12	ENST00000684732.1	c.37+159G>T		intron_variant			NM_001370125.1	ENSP00000508282	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39148 AN: 151954 Hom.: 5428 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.297

GnomAD3 exomes AF: 0.297 AC: 27608 AN: 92844 Hom.: 4905 AF XY: 0.292 AC XY: 13923 AN XY: 47716

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.344

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.637

Gnomad SAS exome AF: 0.191

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.250 AC: 331054 AN: 1325312 Hom.: 44350 Cov.: 31 AF XY: 0.248 AC XY: 160765 AN XY: 647682

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.590

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.257 AC: 39158 AN: 152072 Hom.: 5425 Cov.: 32 AF XY: 0.257 AC XY: 19121 AN XY: 74334

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.293

Alfa AF: 0.251 Hom.: 10435

Bravo AF: 0.275

Asia WGS AF: 0.375 AC: 1301 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	5.9
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000033
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.080		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: rs3865443; hg19: chr19-51537682; COSMIC: COSV51576388; COSMIC: COSV51576388;