dbSNP rs3745535: KLK10:p.Ser50Ala (chr19-51017231-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145888.3(KLK10):c.148T>G(p.Ser50Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,611,012 control chromosomes in the GnomAD database, including 341,466 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.71 ( 40184 hom., cov: 34)

Exomes 𝑓: 0.64 ( 301282 hom. )

Consequence

KLK10
NM_145888.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.15

Variant links:

Genes affected

KLK10 (HGNC:6358): (kallikrein related peptidase 10) 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. Its encoded protein is secreted and may play a role in suppression of tumorigenesis in breast and prostate cancers. Alternate splicing of this gene results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

KLK10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.035569E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK10	NM_145888.3 link	c.148T>G	p.Ser50Ala	missense_variant	Exon 3 of 6	ENST00000358789.8	NP_665895.1	O43240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK10	ENST00000358789.8 link	c.148T>G	p.Ser50Ala	missense_variant	Exon 3 of 6	1	NM_145888.3	ENSP00000351640.2		O43240

Frequencies

GnomAD3 genomes

AF:

0.713

AC:

108456

AN:

152054

Hom.:

40134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.926

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.605

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.459

Gnomad FIN

AF:

0.614

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.635

Gnomad OTH

AF:

0.687

GnomAD3 exomes

AF:

0.637

AC:

153267

AN:

240468

Hom.:

49863

AF XY:

0.624

AC XY:

81840

AN XY:

131190

show subpopulations

Gnomad AFR exome

AF:

0.930

Gnomad AMR exome

AF:

0.666

Gnomad ASJ exome

AF:

0.611

Gnomad EAS exome

AF:

0.651

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.622

Gnomad NFE exome

AF:

0.636

Gnomad OTH exome

AF:

0.630

GnomAD4 exome

AF:

0.639

AC:

932836

AN:

1458840

Hom.:

301282

Cov.:

AF XY:

0.633

AC XY:

459473

AN XY:

725610

show subpopulations

Gnomad4 AFR exome

AF:

0.937

Gnomad4 AMR exome

AF:

0.668

Gnomad4 ASJ exome

AF:

0.613

Gnomad4 EAS exome

AF:

0.629

Gnomad4 SAS exome

AF:

0.483

Gnomad4 FIN exome

AF:

0.619

Gnomad4 NFE exome

AF:

0.643

Gnomad4 OTH exome

AF:

0.651

GnomAD4 genome

AF:

0.713

AC:

108569

AN:

152172

Hom.:

40184

Cov.:

AF XY:

0.707

AC XY:

52623

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.926

Gnomad4 AMR

AF:

0.693

Gnomad4 ASJ

AF:

0.605

Gnomad4 EAS

AF:

0.639

Gnomad4 SAS

AF:

0.460

Gnomad4 FIN

AF:

0.614

Gnomad4 NFE

AF:

0.635

Gnomad4 OTH

AF:

0.683

Alfa

AF:

0.641

Hom.:

64425

Bravo

AF:

0.732

TwinsUK

AF:

0.644

AC:

2389

ALSPAC

AF:

0.640

AC:

2468

ESP6500AA

AF:

0.922

AC:

4053

ESP6500EA

AF:

0.641

AC:

5503

ExAC

AF:

0.636

AC:

76824

Asia WGS

AF:

0.554

AC:

1927

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

3.4

DANN

Benign

0.56

DEOGEN2

Benign

0.14

T;T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.045

.;T;.;T

MetaRNN

Benign

0.0000010

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.70

N;N;N;.

PrimateAI

Benign

0.42

PROVEAN

Benign

0.37

N;N;N;.

REVEL

Benign

0.16

Sift

Benign

0.93

T;T;T;.

Sift4G

Benign

0.84

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.021

MPC

0.14

ClinPred

0.0012

GERP RS

-2.8

Varity_R

0.14

gMVP

0.23

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over