Variant chr19-50979799-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005046.4(KLK7):c.595A>C(p.Asn199His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KLK7
NM_005046.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

KLK7 (HGNC:6368): (kallikrein related peptidase 7) This gene encodes a member of the kallikrein subfamily of serine proteases. These enzymes have diverse physiological functions and many kallikrein genes are biomarkers for cancer. The encoded protein has chymotrypsin-like activity and plays a role in the proteolysis of intercellular cohesive structures that precedes desquamation, the shedding of the outermost layer of the epidermis. The encoded protein may play a role in cancer invasion and metastasis, and increased expression of this gene is associated with unfavorable prognosis and progression of several types of cancer. Polymorphisms in this gene may play a role in the development of atopic dermatitis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is one of fifteen kallikrein subfamily members located in a gene cluster on chromosome 19. [provided by RefSeq, May 2011]

KLK7 links:

(HGNC:):

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	Protein
KLK7	NM_005046.4 linkuse as main transcript	c.595A>C	p.Asn199His	missense_variant	5/6	ENST00000595820.6	NP_005037.1
KLK7	NM_139277.2 linkuse as main transcript	c.595A>C	p.Asn199His	missense_variant	5/6		NP_644806.1
KLK7	NM_001243126.1 linkuse as main transcript	c.574A>C	p.Asn192His	missense_variant	4/5		NP_001230055.1
KLK7	NM_001207053.2 linkuse as main transcript	c.379A>C	p.Asn127His	missense_variant	4/5		NP_001193982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK7	ENST00000595820.6 linkuse as main transcript	c.595A>C	p.Asn199His	missense_variant	5/6	1	NM_005046.4	ENSP00000470538	P1	P49862-1
	ENST00000594512.1 linkuse as main transcript	n.297+6466T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.05e-7

AC:

AN:

1418464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701536

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:

9.18e-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

Nov 03, 2022

The c.595A>C (p.N199H) alteration is located in exon 5 (coding exon 4) of the KLK7 gene. This alteration results from a A to C substitution at nucleotide position 595, causing the asparagine (N) at amino acid position 199 to be replaced by a histidine (H). 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

Pathogenic

0.86

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.62

T;.;T

M_CAP

Pathogenic

0.35

MetaRNN

Uncertain

0.52

D;D;D

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

1.3

L;L;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.7

D;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.0030

D;.;.

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.35

MutPred

0.63

Gain of catalytic residue at N199 (P = 0.116);Gain of catalytic residue at N199 (P = 0.116);.;

MVP

0.98

MPC

0.24

ClinPred

0.94

GERP RS

3.6

Varity_R

0.61

gMVP

0.78

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

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