chr19-50823714-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002257.4(KLK1):āc.35T>Cā(p.Leu12Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 146,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000034 ( 0 hom., cov: 31)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KLK1
NM_002257.4 missense
NM_002257.4 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 0.0620
Genes affected
KLK1 (HGNC:6357): (kallikrein 1) 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. This protein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.747
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLK1 | NM_002257.4 | c.35T>C | p.Leu12Pro | missense_variant | 1/5 | ENST00000301420.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLK1 | ENST00000301420.3 | c.35T>C | p.Leu12Pro | missense_variant | 1/5 | 1 | NM_002257.4 | P1 | |
KLK1 | ENST00000593859.5 | n.74T>C | non_coding_transcript_exon_variant | 1/4 | 2 | ||||
KLK1 | ENST00000593325.5 | c.35T>C | p.Leu12Pro | missense_variant, NMD_transcript_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000342 AC: 5AN: 146330Hom.: 0 Cov.: 31
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1442402Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 718366
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GnomAD4 genome AF: 0.0000342 AC: 5AN: 146330Hom.: 0 Cov.: 31 AF XY: 0.0000280 AC XY: 2AN XY: 71464
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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 09, 2022 | The c.35T>C (p.L12P) alteration is located in exon 1 (coding exon 1) of the KLK1 gene. This alteration results from a T to C substitution at nucleotide position 35, causing the leucine (L) at amino acid position 12 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at