rs150096859

chr2-10046193-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003597.5(KLF11):c.86G>A(p.Arg29Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000542 in 1,614,154 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (2 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.64

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0075652897).
• BP6: Variant 2-10046193-G-A is Benign according to our data. Variant chr2-10046193-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 330622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 288 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF11	NM_003597.5	c.86G>A	p.Arg29Gln	missense_variant	2/4	ENST00000305883.6
KLF11	NM_001177716.2	c.35G>A	p.Arg12Gln	missense_variant	2/4
KLF11	NM_001177718.2	c.35G>A	p.Arg12Gln	missense_variant	2/4
KLF11	XM_047446025.1	c.35G>A	p.Arg12Gln	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF11	ENST00000305883.6	c.86G>A	p.Arg29Gln	missense_variant	2/4	1	NM_003597.5	A2

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 288 AN: 152176 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00141 AC: 354 AN: 251484 Hom.: 0 AF XY: 0.00131 AC XY: 178 AN XY: 135920

Gnomad AFR exome AF: 0.00609

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0124

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.000401 AC: 586 AN: 1461860 Hom.: 2 Cov.: 32 AF XY: 0.000371 AC XY: 270 AN XY: 727236

Gnomad4 AFR exome AF: 0.00636

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00655

Gnomad4 SAS exome AF: 0.000383

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.000911

GnomAD4 genome AF: 0.00190 AC: 289 AN: 152294 Hom.: 1 Cov.: 33 AF XY: 0.00191 AC XY: 142 AN XY: 74460

Gnomad4 AFR AF: 0.00503

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000542 Hom.: 0

Bravo AF: 0.00223

ESP6500AA AF: 0.00499 AC: 22

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00143 AC: 173

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	This variant is associated with the following publications: (PMID: 32041611, 19122346) -

Maturity-onset diabetes of the young type 7 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 24, 2021	- -

Monogenic diabetes Benign:1

Benign, criteria provided, single submitter

research

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Nov 20, 2015

ACMG Criteria: PS3 (PMID:19122346), PP3, BS1 (ExAC, 1000G EAS), BS2 (type2diabetesgenetics.org), BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;.;.;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;D;T;D;T;.
MetaRNN	Benign	0.0076	T;T;T;T;T;T
MetaSVM	Benign	-0.41	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.19	T;T;D;T;T;T
Sift4G	Pathogenic	0.0	D;T;D;T;D;T
Polyphen		1.0	.;D;.;.;.;.
Vest4		0.45, 0.44, 0.43
MVP		0.87
MPC		0.023
ClinPred		0.017	T
GERP RS		1.4
Varity_R		0.073
gMVP		0.14

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

Other links and lift over

dbSNP: rs150096859; hg19: chr2-10186320;