dbSNP rs2075689: KLK10:p.Leu141Leu (chr19-51016003-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_145888.3(KLK10):c.423G>A(p.Leu141Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,567,774 control chromosomes in the GnomAD database, including 242,802 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 27676 hom., cov: 34)

Exomes 𝑓: 0.55 ( 215126 hom. )

Consequence

KLK10
NM_145888.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.355

Publications

17 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP7

Synonymous conserved (PhyloP=0.355 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK10	NM_145888.3 link	c.423G>A	p.Leu141Leu	synonymous_variant	Exon 4 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.423G>A	p.Leu141Leu	synonymous_variant	Exon 4 of 6	1	NM_145888.3	ENSP00000351640.2		O43240

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90633

AN:

152074

Hom.:

27666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.723

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.523

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.573

GnomAD2 exomes

AF:

0.543

AC:

96443

AN:

177642

AF XY:

0.529

show subpopulations

Gnomad AFR exome

AF:

0.719

Gnomad AMR exome

AF:

0.613

Gnomad ASJ exome

AF:

0.519

Gnomad EAS exome

AF:

0.544

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.545

Gnomad OTH exome

AF:

0.544

GnomAD4 exome

AF:

0.548

AC:

776232

AN:

1415582

Hom.:

215126

Cov.:

AF XY:

0.542

AC XY:

379357

AN XY:

699812

show subpopulations

African (AFR)

AF:

0.730

AC:

23746

AN:

32542

American (AMR)

AF:

0.611

AC:

22631

AN:

37020

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

13215

AN:

25312

East Asian (EAS)

AF:

0.466

AC:

17475

AN:

37502

South Asian (SAS)

AF:

0.386

AC:

31101

AN:

80562

European-Finnish (FIN)

AF:

0.555

AC:

27771

AN:

50030

Middle Eastern (MID)

AF:

0.483

AC:

2757

AN:

5712

European-Non Finnish (NFE)

AF:

0.556

AC:

605207

AN:

1088210

Other (OTH)

AF:

0.551

AC:

32329

AN:

58692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

20631

41262

61894

82525

103156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17226

34452

51678

68904

86130

<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:

0.596

AC:

90682

AN:

152192

Hom.:

27676

Cov.:

AF XY:

0.593

AC XY:

44111

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.723

AC:

30011

AN:

41530

American (AMR)

AF:

0.615

AC:

9403

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1819

AN:

3472

East Asian (EAS)

AF:

0.522

AC:

2695

AN:

5164

South Asian (SAS)

AF:

0.370

AC:

1785

AN:

4830

European-Finnish (FIN)

AF:

0.549

AC:

5805

AN:

10582

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.550

AC:

37388

AN:

68000

Other (OTH)

AF:

0.569

AC:

1205

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1911

3823

5734

7646

9557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.561

Hom.:

35653

Bravo

AF:

0.612

Asia WGS

AF:

0.436

AC:

1519

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.7

(source)

DANN

Benign

0.74

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over