Variant 13-73059535-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001730.5(KLF5):c.208C>T(p.Pro70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000386 in 1,035,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

KLF5
NM_001730.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.693

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]

KLF5 links:

KLF5 (HGNC:):

KLF5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07580674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF5	NM_001730.5 linkuse as main transcript	c.208C>T	p.Pro70Ser	missense_variant	1/4	ENST00000377687.6	NP_001721.2	Q13887-1Q5T6X2
KLF5	NM_001286818.2 linkuse as main transcript	c.-12-2326C>T		intron_variant			NP_001273747.1	Q13887-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLF5	ENST00000377687.6 linkuse as main transcript	c.208C>T	p.Pro70Ser	missense_variant	1/4	1	NM_001730.5	ENSP00000366915.4	Q13887-1
KLF5	ENST00000539231.5 linkuse as main transcript	c.-12-2326C>T		intron_variant		1		ENSP00000440407.1	Q13887-4
KLF5	ENST00000477333.5 linkuse as main transcript	n.184-2326C>T		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000386

AC:

AN:

1035330

Hom.:

Cov.:

AF XY:

0.00000203

AC XY:

AN XY:

493442

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000447

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 27, 2023

The c.208C>T (p.P70S) 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 208, causing the proline (P) at amino acid position 70 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

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.4

DANN

Benign

0.95

DEOGEN2

Benign

0.14

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.55

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.67

REVEL

Benign

0.096

Sift

Benign

0.51

Sift4G

Benign

0.55

Polyphen

0.0010

Vest4

0.081

MutPred

0.17

Gain of phosphorylation at P70 (P = 0.0302);

MVP

0.24

MPC

0.22

ClinPred

0.17

GERP RS

4.3

Varity_R

0.032

gMVP

0.20

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over