Variant 13-73059353-G-A 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.26G>A(p.Ser9Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KLF5
NM_001730.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.844

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=0.16276965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF5	NM_001730.5 linkuse as main transcript	c.26G>A	p.Ser9Asn	missense_variant	1/4	ENST00000377687.6	NP_001721.2	Q13887-1Q5T6X2
KLF5	NM_001286818.2 linkuse as main transcript	c.-12-2508G>A		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.26G>A	p.Ser9Asn	missense_variant	1/4	1	NM_001730.5	ENSP00000366915.4	Q13887-1
KLF5	ENST00000539231.5 linkuse as main transcript	c.-12-2508G>A		intron_variant		1		ENSP00000440407.1	Q13887-4
KLF5	ENST00000477333.5 linkuse as main transcript	n.184-2508G>A		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1269170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

624258

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Mar 24, 2023

The c.26G>A (p.S9N) alteration is located in exon 1 (coding exon 1) of the KLF5 gene. This alteration results from a G to A substitution at nucleotide position 26, causing the serine (S) at amino acid position 9 to be replaced by an asparagine (N). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.081

Eigen_PC

Benign

0.068

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

0.060

REVEL

Benign

0.095

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.018

Polyphen

0.15

Vest4

0.12

MutPred

0.16

Loss of phosphorylation at S9 (P = 0.0404);

MVP

0.23

MPC

0.21

ClinPred

0.30

GERP RS

3.7

Varity_R

0.31

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over