Genetic Variant KLF11:p.Phe6Leu (chr2-10043734-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003597.5(KLF11):c.18C>G(p.Phe6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000813 in 1,230,392 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. Synonymous variant affecting the same amino acid position (i.e. F6F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

KLF11
NM_003597.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.220

Publications

0 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:

ENSG00000260077 (HGNC:):

ENSG00000260077 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045241326).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003597.5. 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
	KLF11	NM_003597.5	MANE Select	c.18C>G	p.Phe6Leu	missense	Exon 1 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.-163C>G		upstream_gene	N/A	NP_001171187.1	O14901-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLF11	ENST00000305883.6	TSL:1 MANE Select	c.18C>G	p.Phe6Leu	missense	Exon 1 of 4	ENSP00000307023.1	O14901-1
KLF11	ENST00000921466.1		c.18C>G	p.Phe6Leu	missense	Exon 1 of 3	ENSP00000591525.1
KLF11	ENST00000401510.5	TSL:3	c.-10+663C>G		intron	N/A	ENSP00000386058.1	B5MCC4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.13e-7

AC:

AN:

1230392

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

607498

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23798

American (AMR)

AF:

0.00

AC:

AN:

27902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19194

East Asian (EAS)

AF:

0.00

AC:

AN:

21630

South Asian (SAS)

AF:

0.00

AC:

AN:

73902

European-Finnish (FIN)

AF:

0.0000357

AC:

AN:

28034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3660

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

984714

Other (OTH)

AF:

0.00

AC:

AN:

47558

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.3

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.068

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.26

M_CAP

Benign

0.0088

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.22

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.34

REVEL

Benign

0.0070

Sift

Benign

0.63

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.088

MutPred

0.14

Gain of loop (P = 0.1081)

MVP

0.33

MPC

0.022

ClinPred

0.037

GERP RS

-3.2

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.036

gMVP

0.13

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over