rs148123124

Positions:

chr2-10048119-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/21 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	Protein	UniProt
KLF11	NM_003597.5 link	c.782C>T	p.Pro261Leu	missense_variant	3/4	ENST00000305883.6	NP_003588.1	O14901-1Q53QU8
KLF11	NM_001177716.2 link	c.731C>T	p.Pro244Leu	missense_variant	3/4		NP_001171187.1	O14901-2B7ZAX4
KLF11	NM_001177718.2 link	c.731C>T	p.Pro244Leu	missense_variant	3/4		NP_001171189.1	O14901-2
KLF11	XM_047446025.1 link	c.731C>T	p.Pro244Leu	missense_variant	3/4		XP_047301981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLF11	ENST00000305883.6 link	c.782C>T	p.Pro261Leu	missense_variant	3/4	1	NM_003597.5	ENSP00000307023.1	O14901-1
KLF11	ENST00000535335.1 link	c.731C>T	p.Pro244Leu	missense_variant	3/4	2		ENSP00000442722.1	O14901-2
KLF11	ENST00000540845.5 link	c.731C>T	p.Pro244Leu	missense_variant	3/4	2		ENSP00000444690.1	O14901-2

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

GnomAD3 exomes

AF:

0.00249

AC:

627

AN:

251486

Hom.:

AF XY:

0.00246

AC XY:

335

AN XY:

135920

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 SAS exome

AF:

0.00245

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

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00294

Gnomad4 FIN exome

AF:

0.00603

Gnomad4 NFE exome

AF:

0.00221

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00163

AC:

248

AN:

152316

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.00254

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00220

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

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	KLF11: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 07, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 25, 2016

- -

Monogenic diabetes

Benign:1

Likely benign, criteria provided, single submitter

research

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Feb 17, 2017

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

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;.;.

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

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