chr19-51024783-C-T

Position:

• chr19-51024783-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001136032.3(KLK11):​c.52G>A​(p.Gly18Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLK11 NM_001136032.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.02

Genes affected

KLK11 (HGNC:6359): (kallikrein related peptidase 11) 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. Alternate splicing and the use of alternate promoters results in multiple transcript variants encoding distinct isoforms which are differentially expressed. [provided by RefSeq, Dec 2016]

KLK11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-51024783-C-T is Pathogenic according to our data. Variant chr19-51024783-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2579683.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.40218747). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK11	NM_001136032.3	c.52G>A	p.Gly18Arg	missense_variant	3/6	ENST00000453757.8	NP_001129504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK11	ENST00000453757.8	c.52G>A	p.Gly18Arg	missense_variant	3/6	1	NM_001136032.3	ENSP00000413958.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1431932 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 711826

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ichthyosis with erythrokeratoderma Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0083	.;T;.;.;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.79	.;T;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.40	T;T;T;T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.050	.;N;.;.;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N;.;N;N;.;.
REVEL	Benign	0.25
Sift	Uncertain	0.024	D;.;D;D;.;.
Sift4G	Benign	0.091	T;T;T;T;.;.
Polyphen		0.93	.;P;.;.;.;.
Vest4		0.34
MutPred		0.54		.;Gain of solvent accessibility (P = 0.0456);.;.;.;.;
MVP		0.94
MPC		0.35
ClinPred		0.51	D
GERP RS		3.0
Varity_R		0.081
gMVP		0.48

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.

Other links and lift over

hg19: chr19-51528039;