Genetic Variant KLK13:p.Arg150His (chr19-51059884-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015596.3(KLK13):c.449G>A(p.Arg150His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,603,358 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

KLK13
NM_015596.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.971

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10208127).

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.449G>A	p.Arg150His	missense	Exon 3 of 5	NP_056411.1	Q9UKR3-1
KLK13	NM_001348177.2		c.289+160G>A		intron	N/A	NP_001335106.1	Q86VI7
KLK13	NM_001348178.2		c.53-1210G>A		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.449G>A	p.Arg150His	missense	Exon 3 of 5	ENSP00000470555.1	Q9UKR3-1
KLK13	ENST00000596955.1	TSL:1	c.449G>A	p.Arg150His	missense	Exon 3 of 3	ENSP00000472248.1	M0R218
KLK13	ENST00000595547.5	TSL:1	c.289+160G>A		intron	N/A	ENSP00000470245.1	Q86VI7

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000291

AC:

AN:

240610

AF XY:

0.0000232

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000920

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.00000896

AC:

AN:

1451402

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

721146

show subpopulations

African (AFR)

AF:

0.0000901

AC:

AN:

33314

American (AMR)

AF:

0.00

AC:

AN:

43786

Ashkenazi Jewish (ASJ)

AF:

0.0000398

AC:

AN:

25138

East Asian (EAS)

AF:

0.00

AC:

AN:

39538

South Asian (SAS)

AF:

0.00

AC:

AN:

84416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00000633

AC:

AN:

1106578

Other (OTH)

AF:

0.0000334

AC:

AN:

59926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000526

AC:

AN:

151956

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.0000725

AC:

AN:

41360

American (AMR)

AF:

0.000197

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.594

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000761

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

AC:

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

0.074

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.17

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.81

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.14

M_CAP

Benign

0.0088

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

0.97

PrimateAI

Benign

0.23

Sift4G

Benign

0.56

Polyphen

0.094

Vest4

0.19

MVP

0.41

MPC

0.12

ClinPred

0.060

GERP RS

1.6

Varity_R

0.029

gMVP

0.37

Mutation Taster

=92/8

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

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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