Variant 19-50821863-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002257.4(KLK1):c.55C>A(p.Pro19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,100 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KLK1
NM_002257.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.775

Variant links:

Genes affected

KLK1 (HGNC:6357): (kallikrein 1) 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. This protein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. [provided by RefSeq, Jul 2008]

KLK1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK1	NM_002257.4 linkuse as main transcript	c.55C>A	p.Pro19Thr	missense_variant	2/5	ENST00000301420.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK1	ENST00000301420.3 linkuse as main transcript	c.55C>A	p.Pro19Thr	missense_variant	2/5	1	NM_002257.4	P1	P06870-1
KLK1	ENST00000593859.5 linkuse as main transcript	n.94C>A		non_coding_transcript_exon_variant	2/4	2
KLK1	ENST00000593325.5 linkuse as main transcript	c.*864C>A		3_prime_UTR_variant, NMD_transcript_variant	3/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724342

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 10, 2022

The c.55C>A (p.P19T) alteration is located in exon 2 (coding exon 2) of the KLK1 gene. This alteration results from a C to A substitution at nucleotide position 55, causing the proline (P) at amino acid position 19 to be replaced by a threonine (T). 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

-0.035

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.76

M_CAP

Benign

0.077

MetaRNN

Uncertain

0.49

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.17

Sift

Uncertain

0.0030

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.41

MutPred

0.31

Gain of phosphorylation at P19 (P = 0.0388);

MVP

0.76

MPC

0.50

ClinPred

0.52

GERP RS

0.94

Varity_R

0.15

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over