Variant 19-51024219-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001136032.3(KLK11):c.289G>A(p.Gly97Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

KLK11
NM_001136032.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

KLK11 (HGNC:6359): (kallikrein related peptidase 11) 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 and the use of alternate promoters results in multiple transcript variants encoding distinct isoforms which are differentially expressed. [provided by RefSeq, Dec 2016]

KLK11 links:

KLK11 (HGNC:):

KLK11 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK11	NM_001136032.3 linkuse as main transcript	c.289G>A	p.Gly97Ser	missense_variant	4/6	ENST00000453757.8	NP_001129504.1	Q9UBX7-1A0A1R3UDR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK11	ENST00000453757.8 linkuse as main transcript	c.289G>A	p.Gly97Ser	missense_variant	4/6	1	NM_001136032.3	ENSP00000413958.2		Q9UBX7-1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000219

AC:

AN:

250998

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00136

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.0000706

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000173

AC:

253

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

121

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00378

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.0000522

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000191

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000151

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.000264

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.385G>A (p.G129S) alteration is located in exon 4 (coding exon 4) of the KLK11 gene. This alteration results from a G to A substitution at nucleotide position 385, causing the glycine (G) at amino acid position 129 to be replaced by a serine (S). 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

0.093

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.079

.;T;.;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.40

.;T;T;T;T

M_CAP

Benign

0.070

MetaRNN

Benign

0.040

T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.040

.;N;.;.;.

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.7

N;.;N;N;.

REVEL

Uncertain

0.29

Sift

Benign

0.31

T;.;T;T;.

Sift4G

Benign

0.73

T;T;T;T;.

Polyphen

0.62

.;P;.;.;.

Vest4

0.092

MVP

0.90

MPC

0.11

ClinPred

0.037

GERP RS

4.3

Varity_R

0.18

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.32

Position offset: -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