GeneBe

rs374835129

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012427.5(KLK5):​c.652G>C​(p.Glu218Gln) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E218K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

KLK5
NM_012427.5 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.804

Publications

1 publications found
Variant links:
Genes affected
KLK5 (HGNC:6366): (kallikrein related peptidase 5) 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. Its expression is up-regulated by estrogens and progestins. The encoded protein is secreted and may be involved in desquamation in the epidermis. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07996476).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012427.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
KLK5
NM_012427.5
MANE Select
c.652G>Cp.Glu218Gln
missense
Exon 5 of 6NP_036559.1Q9Y337
KLK5
NM_001077491.2
c.652G>Cp.Glu218Gln
missense
Exon 6 of 7NP_001070959.1Q9Y337
KLK5
NM_001077492.2
c.652G>Cp.Glu218Gln
missense
Exon 5 of 6NP_001070960.1Q9Y337

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
KLK5
ENST00000336334.8
TSL:1 MANE Select
c.652G>Cp.Glu218Gln
missense
Exon 5 of 6ENSP00000337733.2Q9Y337
KLK5
ENST00000391809.6
TSL:1
c.652G>Cp.Glu218Gln
missense
Exon 6 of 7ENSP00000375685.1Q9Y337
KLK5
ENST00000593428.5
TSL:1
c.652G>Cp.Glu218Gln
missense
Exon 5 of 6ENSP00000471966.1Q9Y337

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
0.43
DANN
Benign
0.55
DEOGEN2
Benign
0.27
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.056
T
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-0.69
T
MutationAssessor
Benign
0.040
N
PhyloP100
-0.80
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.58
N
REVEL
Benign
0.13
Sift
Benign
0.25
T
Sift4G
Benign
0.27
T
Polyphen
0.040
B
Vest4
0.064
MutPred
0.26
Loss of ubiquitination at K215 (P = 0.0396)
MVP
0.86
MPC
0.099
ClinPred
0.063
T
GERP RS
-1.5
Varity_R
0.086
gMVP
0.61
Mutation Taster
=96/4
polymorphism

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

Other links and lift over

dbSNP: rs374835129; hg19: chr19-51451970; API