rs587780378

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003597.5(KLF11):c.467G>T(p.Gly156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 1 hom. )

Consequence

KLF11
NM_003597.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.331

Publications

1 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022491246).

BP6

Variant 2-10047804-G-T is Benign according to our data. Variant chr2-10047804-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 129432.

BS2

High AC in GnomAdExome4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5 link	c.467G>T	p.Gly156Val	missense_variant	Exon 3 of 4	ENST00000305883.6	NP_003588.1	O14901-1Q53QU8
KLF11	NM_001177716.2 link	c.416G>T	p.Gly139Val	missense_variant	Exon 3 of 4		NP_001171187.1	O14901-2B7ZAX4
KLF11	NM_001177718.2 link	c.416G>T	p.Gly139Val	missense_variant	Exon 3 of 4		NP_001171189.1	O14901-2
KLF11	XM_047446025.1 link	c.416G>T	p.Gly139Val	missense_variant	Exon 3 of 4		XP_047301981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6 link	c.467G>T	p.Gly156Val	missense_variant	Exon 3 of 4	1	NM_003597.5	ENSP00000307023.1		O14901-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000143

AC:

AN:

251052

AF XY:

0.000125

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00101

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:

0.000163

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461372

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726988

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000850

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111960

Other (OTH)

AF:

0.0000166

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000472

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Jun 27, 2013

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Uncertain:1

Oct 19, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.467G>T (p.G156V) alteration is located in exon 3 (coding exon 3) of the KLF11 gene. This alteration results from a G to T substitution at nucleotide position 467, causing the glycine (G) at amino acid position 156 to be replaced by a valine (V). 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

Benign

0.15

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.35

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.20

T;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.49

T;T;T;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.022

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

M;.;.;.

PhyloP100

0.33

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.067

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.012

B;.;.;.

Vest4

0.13

MutPred

0.30

Loss of methylation at R155 (P = 0.0554);.;.;.;

MVP

0.57

MPC

0.023

ClinPred

0.033

GERP RS

-0.96

Varity_R

0.053

gMVP

0.35

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over