rs148123124

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003597.5(KLF11):c.782C>T(p.Pro261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,614,198 control chromosomes in the GnomAD database, including 16 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 16 hom. )

Consequence

KLF11
NM_003597.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.93

Publications

8 publications found

Variant links:

Genes affected

KLF11 (HGNC:11811): (KLF transcription factor 11) The protein encoded by this gene is a zinc finger transcription factor that binds to SP1-like sequences in epsilon- and gamma-globin gene promoters. This binding inhibits cell growth and causes apoptosis. Defects in this gene are a cause of maturity-onset diabetes of the young type 7 (MODY7). Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

KLF11 Gene-Disease associations (from GenCC):

maturity-onset diabetes of the young type 7
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
maturity-onset diabetes of the young
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
monogenic diabetes
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KLF11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00955826).

BP6

Variant 2-10048119-C-T is Benign according to our data. Variant chr2-10048119-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 330631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5 link	c.782C>T	p.Pro261Leu	missense_variant	Exon 3 of 4	ENST00000305883.6	NP_003588.1	O14901-1Q53QU8
KLF11	NM_001177716.2 link	c.731C>T	p.Pro244Leu	missense_variant	Exon 3 of 4		NP_001171187.1	O14901-2B7ZAX4
KLF11	NM_001177718.2 link	c.731C>T	p.Pro244Leu	missense_variant	Exon 3 of 4		NP_001171189.1	O14901-2
KLF11	XM_047446025.1 link	c.731C>T	p.Pro244Leu	missense_variant	Exon 3 of 4		XP_047301981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KLF11	ENST00000305883.6 link	c.782C>T	p.Pro261Leu	missense_variant	Exon 3 of 4	1	NM_003597.5	ENSP00000307023.1	O14901-1
KLF11	ENST00000535335.1 link	c.731C>T	p.Pro244Leu	missense_variant	Exon 3 of 4	2		ENSP00000442722.1	O14901-2
KLF11	ENST00000540845.5 link	c.731C>T	p.Pro244Leu	missense_variant	Exon 3 of 4	2		ENSP00000444690.1	O14901-2
KLF11	ENST00000448523.5 link	c.*240C>T		downstream_gene_variant		4		ENSP00000387866.1	E7EX78

Frequencies

GnomAD3 genomes

AF:

0.00163

AC:

248

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00249

AC:

627

AN:

251486

AF XY:

0.00246

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00573

Gnomad NFE exome

AF:

0.00364

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00215

AC:

3146

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1595

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33480

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00294

AC:

254

AN:

86258

European-Finnish (FIN)

AF:

0.00603

AC:

322

AN:

53416

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00221

AC:

2458

AN:

1112004

Other (OTH)

AF:

0.00157

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

207

413

620

826

1033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.00163

AC:

248

AN:

152316

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41558

American (AMR)

AF:

0.000327

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00509

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00254

AC:

173

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.00227

Hom.:

Bravo

AF:

0.00108

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00317

AC:

385

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00243

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KLF11: BP4, BS2 -

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 25, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Monogenic diabetes

Benign:1

Feb 17, 2017

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

ACMG Criteria:PP3 (5 predictors), BP4 (5 predictors), BS2 (27 cases and 37 controls in type2diabetesgenetics.org) -

Maturity-onset diabetes of the young type 7

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Uncertain

0.43

T;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.028

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

T;T;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.0096

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;.

PhyloP100

1.9

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.5

D;D;D

REVEL

Benign

0.15

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.096

T;T;T

Polyphen

0.0060

B;.;.

Vest4

0.28

MVP

0.57

MPC

0.027

ClinPred

0.041

GERP RS

4.2

Varity_R

0.22

gMVP

0.44

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over