rs3865443

Variant names:

• chr19-51034426-C-A
• rs3865443
• ENST00000526824.5:n.196G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000526824.5(KLK12):​n.196G>T variant causes a splice region, non coding transcript exon 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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 ENST00000526824.5 splice_region, non_coding_transcript_exon
• Scores: Splicing: ADA: 0.00003319
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 9 publications found

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]

ENSG00000268906 (HGNC:):

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 = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526824.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK12	NM_001370125.1	MANE Select	c.37+159G>T		intron	N/A	NP_001357054.1
	KLK12	NM_001370126.1		c.-35G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001357055.1
	KLK12	NM_001370128.1		c.-35G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001357057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK12	ENST00000526824.5	TSL:1	n.196G>T		splice_region non_coding_transcript_exon	Exon 2 of 6	ENSP00000434604.1
	KLK12	ENST00000530943.6	TSL:1	n.196G>T		splice_region non_coding_transcript_exon	Exon 2 of 5	ENSP00000434339.1
	KLK12	ENST00000684732.1	MANE Select	c.37+159G>T		intron	N/A	ENSP00000508282.1

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

GnomAD2 exomes AF: 0.297 AC: 27608 AN: 92844 AF XY: 0.292

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 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

African (AFR) AF: 0.226 AC: 6732 AN: 29732

American (AMR) AF: 0.349 AC: 9619 AN: 27560

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 5487 AN: 20694

East Asian (EAS) AF: 0.590 AC: 20847 AN: 35306

South Asian (SAS) AF: 0.188 AC: 12761 AN: 68014

European-Finnish (FIN) AF: 0.185 AC: 6387 AN: 34610

Middle Eastern (MID) AF: 0.260 AC: 1370 AN: 5272

European-Non Finnish (NFE) AF: 0.241 AC: 252918 AN: 1048866

Other (OTH) AF: 0.270 AC: 14933 AN: 55258

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

African (AFR) AF: 0.227 AC: 9432 AN: 41478

American (AMR) AF: 0.336 AC: 5141 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3128 AN: 5136

South Asian (SAS) AF: 0.199 AC: 957 AN: 4816

European-Finnish (FIN) AF: 0.176 AC: 1868 AN: 10592

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16717 AN: 67982

Other (OTH) AF: 0.293 AC: 619 AN: 2112

Alfa AF: 0.253 Hom.: 22063

Bravo AF: 0.275

Asia WGS AF: 0.375 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.29
PhyloP100		0.043
PromoterAI		0.011	Neutral
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3865443; hg19: chr19-51537682; COSMIC: COSV51576388; COSMIC: COSV51576388;