Genetic Variant NM_001730.5:c.218C>T (chr13-73059545-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001730.5(KLF5):c.218C>T(p.Pro73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000408 in 1,176,118 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

KLF5
NM_001730.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034586191).

BS2

High AC in GnomAd4 at 28 AD gene.

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>T	p.Pro73Leu	missense	Exon 1 of 4	NP_001721.2
	KLF5	NM_001286818.2		c.-12-2316C>T		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>T	p.Pro73Leu	missense	Exon 1 of 4	ENSP00000366915.4	Q13887-1
KLF5	ENST00000539231.5	TSL:1	c.-12-2316C>T		intron	N/A	ENSP00000440407.1	Q13887-4
KLF5	ENST00000851191.1		c.218C>T	p.Pro73Leu	missense	Exon 1 of 3	ENSP00000521250.1

Frequencies

GnomAD3 genomes

AF:

0.000186

AC:

AN:

150800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000630

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00195

AC:

AN:

512

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0714

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000195

AC:

AN:

1025210

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

488652

show subpopulations

African (AFR)

AF:

0.000879

AC:

AN:

20468

American (AMR)

AF:

0.000157

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:

0.00

AC:

AN:

888636

Other (OTH)

AF:

0.0000257

AC:

AN:

38868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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

AF:

0.000186

AC:

AN:

150908

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

73690

show subpopulations

African (AFR)

AF:

0.000628

AC:

AN:

41408

American (AMR)

AF:

0.000132

AC:

AN:

15142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67546

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000162

Asia WGS

AF:

0.000296

AC:

AN:

3396

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.9

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.14

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-0.71

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.35

REVEL

Benign

0.031

Sift

Uncertain

0.012

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.14

MutPred

0.30

Loss of glycosylation at P73 (P = 0.023)

MVP

0.10

MPC

0.77

ClinPred

0.083

GERP RS

1.3

Varity_R

0.052

gMVP

0.18

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over