rs144431930

Positions:

chr2-10048290-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_003597.5(KLF11):c.953T>G(p.Leu318Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000886 in 1,602,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

KLF11
NM_003597.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.44

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19262105).

BP6

Variant 2-10048290-T-G is Benign according to our data. Variant chr2-10048290-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 393368.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr2-10048290-T-G is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 69 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLF11	NM_003597.5 linkuse as main transcript	c.953T>G	p.Leu318Arg	missense_variant	3/4	ENST00000305883.6	NP_003588.1
KLF11	NM_001177716.2 linkuse as main transcript	c.902T>G	p.Leu301Arg	missense_variant	3/4		NP_001171187.1
KLF11	NM_001177718.2 linkuse as main transcript	c.902T>G	p.Leu301Arg	missense_variant	3/4		NP_001171189.1
KLF11	XM_047446025.1 linkuse as main transcript	c.902T>G	p.Leu301Arg	missense_variant	3/4		XP_047301981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6 linkuse as main transcript	c.953T>G	p.Leu318Arg	missense_variant	3/4	1	NM_003597.5	ENSP00000307023	A2	O14901-1
KLF11	ENST00000535335.1 linkuse as main transcript	c.902T>G	p.Leu301Arg	missense_variant	3/4	2		ENSP00000442722	P4	O14901-2
KLF11	ENST00000540845.5 linkuse as main transcript	c.902T>G	p.Leu301Arg	missense_variant	3/4	2		ENSP00000444690	P4	O14901-2

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.000132

AC:

AN:

242340

Hom.:

AF XY:

0.0000997

AC XY:

AN XY:

130454

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.0000587

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000504

AC:

AN:

1449698

Hom.:

Cov.:

AF XY:

0.0000459

AC XY:

AN XY:

719710

show subpopulations

Gnomad4 AFR exome

AF:

0.00174

Gnomad4 AMR exome

AF:

0.0000680

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000362

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.000453

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000146

Hom.:

Bravo

AF:

0.000616

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Monogenic diabetes

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Feb 12, 2016

ACMG Criteria: PP3, BP4 -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 24, 2023

- -

Maturity-onset diabetes of the young type 7

Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

T;T;.

M_CAP

Benign

0.051

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.9

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.83

MVP

0.78

MPC

0.19

ClinPred

0.22

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.65

gMVP

0.48

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