chr19-51023118-G-C

Position:

• chr19-51023118-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136032.3(KLK11):​c.574C>G​(p.Gln192Glu) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLK11 NM_001136032.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.142

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058850676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK11	NM_001136032.3	c.574C>G	p.Gln192Glu	missense_variant	5/6	ENST00000453757.8	NP_001129504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK11	ENST00000453757.8	c.574C>G	p.Gln192Glu	missense_variant	5/6	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

Dec 10, 2024

The c.670C>G (p.Q224E) alteration is located in exon 5 (coding exon 5) of the KLK11 gene. This alteration results from a C to G substitution at nucleotide position 670, causing the glutamine (Q) at amino acid position 224 to be replaced by a glutamic acid (E). 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	0.062
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.21
DANN	Benign	0.65
DEOGEN2	Benign	0.15	T;.;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.68	T;.;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.059	T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	-0.59	.;.;N;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.43	.;N;.;N;N
REVEL	Benign	0.25
Sift	Benign	1.0	.;T;.;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	.;.;B;.;.
Vest4		0.099
MutPred		0.44		.;.;Gain of disorder (P = 0.0997);.;.;
MVP		0.77
MPC		0.092
ClinPred		0.055	T
GERP RS		-1.6
Varity_R		0.036
gMVP		0.44

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: chr19-51526374;