dbSNP rs3865443: KLK12:n.196G>T (chr19-51034426-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Variant links:

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]

KLK12 links:

ENSG00000268906 (HGNC:):

ENSG00000268906 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK12	NM_001370125.1 link	c.37+159G>T		intron_variant	Intron 2 of 5	ENST00000684732.1	NP_001357054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK12	ENST00000684732.1 link	c.37+159G>T		intron_variant	Intron 2 of 5		NM_001370125.1	ENSP00000508282.1		Q9UKR0-1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39148

AN:

151954

Hom.:

5428

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.248

AC XY:

160765

AN XY:

647682

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

11835

23669

35504

47338

59173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.257

AC:

39158

AN:

152072

Hom.:

5425

Cov.:

AF XY:

0.257

AC XY:

19121

AN XY:

74334

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16717

AN:

67982

Other (OTH)

AF:

0.293

AC:

619

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1474

2948

4421

5895

7369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.9

(source)

DANN

Benign

0.29

PhyloP100

0.043

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

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

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rs3865443

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over