dbSNP rs557353198: KLF5:p.Pro73Gln (chr13-73059545-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001730.5(KLF5):c.218C>A(p.Pro73Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000975 in 1,025,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P73L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.8e-7 ( 0 hom. )

Consequence

KLF5
NM_001730.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.713

Publications

0 publications found

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:

Genome browser will be placed here

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=0.083989054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001730.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF5	NM_001730.5	MANE Select	c.218C>A	p.Pro73Gln	missense	Exon 1 of 4	NP_001721.2
	KLF5	NM_001286818.2		c.-12-2316C>A		intron	N/A	NP_001273747.1	Q13887-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLF5	ENST00000377687.6	TSL:1 MANE Select	c.218C>A	p.Pro73Gln	missense	Exon 1 of 4	ENSP00000366915.4	Q13887-1
KLF5	ENST00000539231.5	TSL:1	c.-12-2316C>A		intron	N/A	ENSP00000440407.1	Q13887-4
KLF5	ENST00000851191.1		c.218C>A	p.Pro73Gln	missense	Exon 1 of 3	ENSP00000521250.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.75e-7

AC:

AN:

1025210

Hom.:

Cov.:

AF XY:

0.00000205

AC XY:

AN XY:

488652

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20468

American (AMR)

AF:

0.00

AC:

AN:

6352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11192

East Asian (EAS)

AF:

0.00

AC:

AN:

19414

South Asian (SAS)

AF:

0.00

AC:

AN:

20300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2568

European-Non Finnish (NFE)

AF:

0.00000113

AC:

AN:

888636

Other (OTH)

AF:

0.00

AC:

AN:

38868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.66

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.14

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

PhyloP100

-0.71

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.44

REVEL

Benign

0.038

Sift

Benign

0.28

Sift4G

Benign

0.51

Polyphen

0.0

Vest4

0.17

MutPred

0.27

Loss of catalytic residue at P73 (P = 0.0018)

MVP

0.23

MPC

0.78

ClinPred

0.18

GERP RS

1.3

Varity_R

0.037

gMVP

0.21

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over