Variant 19-51082721-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001369775.2(KLK14):c.-23+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,613,948 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 7 hom., cov: 30)

Exomes 𝑓: 0.016 ( 248 hom. )

Consequence

KLK14
NM_001369775.2 splice_donor

Scores

Splicing: ADA: 0.9999

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0260

Variant links:

Genes affected

KLK14 (HGNC:6362): (kallikrein related peptidase 14) This gene encodes a member of the kallikrein subfamily of serine proteases that have diverse physiological functions such as regulation of blood pressure and desquamation. The altered expression of this gene is implicated in the progression of different cancers including breast and prostate tumors. The encoded protein is a precursor that is proteolytically processed to generate the functional enzyme. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

KLK14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 19-51082721-C-T is Benign according to our data. Variant chr19-51082721-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 808632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00965 (1469/152160) while in subpopulation SAS AF= 0.0328 (158/4816). AF 95% confidence interval is 0.0286. There are 7 homozygotes in gnomad4. There are 738 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK14	NM_001369775.2 linkuse as main transcript	c.-23+1G>A		splice_donor_variant		ENST00000650543.2	NP_001356704.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
KLK14	ENST00000650543.2 linkuse as main transcript	c.-23+1G>A	splice_donor_variant		NM_001369775.2	ENSP00000497141	P1
KLK14	ENST00000156499.7 linkuse as main transcript	c.-23+1G>A	splice_donor_variant	1		ENSP00000156499	P1
KLK14	ENST00000391802.1 linkuse as main transcript	c.26+1G>A	splice_donor_variant	5		ENSP00000375678

Frequencies

GnomAD3 genomes

AF:

0.00966

AC:

1468

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0328

Gnomad FIN

AF:

0.00650

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.0135

AC:

3368

AN:

249204

Hom.:

AF XY:

0.0149

AC XY:

2019

AN XY:

135262

show subpopulations

Gnomad AFR exome

AF:

0.00278

Gnomad AMR exome

AF:

0.00562

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0332

Gnomad FIN exome

AF:

0.00798

Gnomad NFE exome

AF:

0.0164

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0155

AC:

22661

AN:

1461788

Hom.:

248

Cov.:

AF XY:

0.0162

AC XY:

11815

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.00566

Gnomad4 ASJ exome

AF:

0.00187

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0349

Gnomad4 FIN exome

AF:

0.00813

Gnomad4 NFE exome

AF:

0.0163

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

AF:

0.00965

AC:

1469

AN:

152160

Hom.:

Cov.:

AF XY:

0.00992

AC XY:

738

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0328

Gnomad4 FIN

AF:

0.00650

Gnomad4 NFE

AF:

0.0152

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.0138

Hom.:

Bravo

AF:

0.00872

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0161

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0147

AC:

123

ExAC

AF:

0.0148

AC:

1794

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0122

EpiControl

AF:

0.0165

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.74

Eigen

Benign

0.10

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.030

MutationTaster

Benign

1.0

D;D

GERP RS

-0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.74

SpliceAI score (max)

0.84

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.84

Position offset: 1

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