Variant 19-51059984-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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:

KLK13 (HGNC:):

KLK13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK13	NM_015596.3 linkuse as main transcript	c.349A>C	p.Thr117Pro	missense_variant	3/5	ENST00000595793.6	NP_056411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK13	ENST00000595793.6 linkuse as main transcript	c.349A>C	p.Thr117Pro	missense_variant	3/5	1	NM_015596.3	ENSP00000470555.1		Q9UKR3-1

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

GnomAD3 exomes

AF:

0.000634

AC:

159

AN:

250626

Hom.:

AF XY:

0.000642

AC XY:

AN XY:

135460

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 SAS 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

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.000664

AC:

101

AN:

152166

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00105

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.349A>C (p.T117P) alteration is located in exon 3 (coding exon 3) of the KLK13 gene. This alteration results from a A to C substitution at nucleotide position 349, causing the threonine (T) at amino acid position 117 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.79

N;.

PrimateAI

Benign

0.37

Sift4G

Benign

0.47

T;T

Polyphen

0.096

B;.

Vest4

0.38

MVP

0.59

MPC

0.58

ClinPred

0.022

GERP RS

3.9

Varity_R

0.15

gMVP

0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over