13-73059382-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001730.5(KLF5):​c.55C>T​(p.Pro19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000673 in 1,410,630 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

KLF5
NM_001730.5 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31
Variant links:
Genes affected
KLF5 (HGNC:6349): (KLF transcription factor 5) This gene encodes a member of the Kruppel-like factor subfamily of zinc finger proteins. The encoded protein is a transcriptional activator that binds directly to a specific recognition motif in the promoters of target genes. This protein acts downstream of multiple different signaling pathways and is regulated by post-translational modification. It may participate in both promoting and suppressing cell proliferation. Expression of this gene may be changed in a variety of different cancers and in cardiovascular disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.093821794).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLF5NM_001730.5 linkc.55C>T p.Pro19Ser missense_variant 1/4 ENST00000377687.6 NP_001721.2 Q13887-1Q5T6X2
KLF5NM_001286818.2 linkc.-12-2479C>T intron_variant NP_001273747.1 Q13887-4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLF5ENST00000377687.6 linkc.55C>T p.Pro19Ser missense_variant 1/41 NM_001730.5 ENSP00000366915.4 Q13887-1
KLF5ENST00000539231.5 linkc.-12-2479C>T intron_variant 1 ENSP00000440407.1 Q13887-4
KLF5ENST00000477333.5 linkn.184-2479C>T intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000397
AC:
6
AN:
151200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000594
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000404
AC:
2
AN:
49546
Hom.:
0
AF XY:
0.0000699
AC XY:
2
AN XY:
28614
show subpopulations
Gnomad AFR exome
AF:
0.00148
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000546
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000707
AC:
89
AN:
1259430
Hom.:
0
Cov.:
30
AF XY:
0.0000615
AC XY:
38
AN XY:
618272
show subpopulations
Gnomad4 AFR exome
AF:
0.0000389
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:
0.0000768
Gnomad4 OTH exome
AF:
0.000195
GnomAD4 genome
AF:
0.0000397
AC:
6
AN:
151200
Hom.:
0
Cov.:
32
AF XY:
0.0000407
AC XY:
3
AN XY:
73752
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000594
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000378

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 submitterclinical testingAmbry GeneticsNov 17, 2022The c.55C>T (p.P19S) alteration is located in exon 1 (coding exon 1) of the KLF5 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the proline (P) at amino acid position 19 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
0.12
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T
Eigen
Benign
-0.16
Eigen_PC
Benign
0.041
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.76
T
M_CAP
Pathogenic
0.46
D
MetaRNN
Benign
0.094
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.3
L
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
0.16
N
REVEL
Benign
0.023
Sift
Uncertain
0.0030
D
Sift4G
Benign
0.074
T
Polyphen
0.0080
B
Vest4
0.15
MutPred
0.18
Loss of catalytic residue at P18 (P = 0.0264);
MVP
0.36
MPC
0.23
ClinPred
0.15
T
GERP RS
4.6
Varity_R
0.11
gMVP
0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs990595749; hg19: chr13-73633520; API