Genetic Variant KLK13:p.Thr117Pro (chr19-51059984-T-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015596.3(KLK13):c.349A>C(p.Thr117Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000982 in 1,613,534 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 5 hom. )

Consequence

KLK13
NM_015596.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Publications

1 publications found

Variant links:

Genes affected

KLK13 (HGNC:6361): (kallikrein related peptidase 13) 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. Expression of this gene is regulated by steroid hormones and may be useful as a marker for breast cancer. [provided by RefSeq, Jan 2017]

KLK13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028006166).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015596.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLK13	NM_015596.3	MANE Select	c.349A>C	p.Thr117Pro	missense	Exon 3 of 5	NP_056411.1	Q9UKR3-1
KLK13	NM_001348177.2		c.289+60A>C		intron	N/A	NP_001335106.1	Q86VI7
KLK13	NM_001348178.2		c.53-1310A>C		intron	N/A	NP_001335107.1	Q9UKR3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLK13	ENST00000595793.6	TSL:1 MANE Select	c.349A>C	p.Thr117Pro	missense	Exon 3 of 5	ENSP00000470555.1	Q9UKR3-1
KLK13	ENST00000596955.1	TSL:1	c.349A>C	p.Thr117Pro	missense	Exon 3 of 3	ENSP00000472248.1	M0R218
KLK13	ENST00000595547.5	TSL:1	c.289+60A>C		intron	N/A	ENSP00000470245.1	Q86VI7

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000634

AC:

159

AN:

250626

AF XY:

0.000642

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.00102

AC:

1484

AN:

1461368

Hom.:

Cov.:

AF XY:

0.000952

AC XY:

692

AN XY:

727008

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33464

American (AMR)

AF:

0.000604

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00125

AC:

1392

AN:

1111682

Other (OTH)

AF:

0.000779

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000664

AC:

101

AN:

152166

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41500

American (AMR)

AF:

0.000392

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00129

AC:

AN:

67978

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000931

Hom.:

Bravo

AF:

0.000669

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000560

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.18

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.58

M_CAP

Benign

0.029

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.79

PhyloP100

1.3

PrimateAI

Benign

0.37

Sift4G

Benign

0.47

Polyphen

0.096

Vest4

0.38

MVP

0.59

MPC

0.58

ClinPred

0.022

GERP RS

3.9

Varity_R

0.15

gMVP

0.76

Mutation Taster

=80/20

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over