chr19-51024182-T-C

Position:

• chr19-51024182-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001136032.3(KLK11):​c.326A>G​(p.Asn109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLK11 NM_001136032.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK11	NM_001136032.3	c.326A>G	p.Asn109Ser	missense_variant	4/6	ENST00000453757.8	NP_001129504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK11	ENST00000453757.8	c.326A>G	p.Asn109Ser	missense_variant	4/6	1	NM_001136032.3	ENSP00000413958.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2023

The c.422A>G (p.N141S) alteration is located in exon 4 (coding exon 4) of the KLK11 gene. This alteration results from a A to G substitution at nucleotide position 422, causing the asparagine (N) at amino acid position 141 to be replaced by a serine (S). 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	0.25
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	.;T;.;.;D
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	.;T;T;T;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.88	D;D;D;D;D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	1.9	.;M;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.9	D;.;D;D;.
REVEL	Uncertain	0.48
Sift	Benign	0.031	D;.;D;D;.
Sift4G	Uncertain	0.039	D;T;D;D;.
Polyphen		0.83	.;P;.;.;.
Vest4		0.59
MutPred		0.82		.;Gain of phosphorylation at N141 (P = 0.0662);.;.;.;
MVP		0.97
MPC		0.33
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.33
gMVP		0.45

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: chr19-51527438;