rs150096859

Variant names:

• chr2-10046193-G-A
• rs150096859
• NM_003597.5:c.86G>A

Variant summary

Our verdict is Benign. The variant received -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:6
• Conservation: PhyloP100: 3.64
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 330622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 289 AD gene.

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.86G>A	p.Arg29Gln	missense	Exon 2 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.35G>A	p.Arg12Gln	missense	Exon 2 of 4	NP_001171187.1	O14901-2
	KLF11	NM_001177718.2		c.35G>A	p.Arg12Gln	missense	Exon 2 of 4	NP_001171189.1	O14901-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.86G>A	p.Arg29Gln	missense	Exon 2 of 4	ENSP00000307023.1	O14901-1
	KLF11	ENST00000535335.1	TSL:2	c.35G>A	p.Arg12Gln	missense	Exon 2 of 4	ENSP00000442722.1	O14901-2
	KLF11	ENST00000540845.5	TSL:2	c.35G>A	p.Arg12Gln	missense	Exon 2 of 4	ENSP00000444690.1	O14901-2

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

GnomAD2 exomes AF: 0.00141 AC: 354 AN: 251484 AF XY: 0.00131

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 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

African (AFR) AF: 0.00636 AC: 213 AN: 33478

American (AMR) AF: 0.000246 AC: 11 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00655 AC: 260 AN: 39700

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5744

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1112006

Other (OTH) AF: 0.000911 AC: 55 AN: 60394

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

African (AFR) AF: 0.00503 AC: 209 AN: 41572

American (AMR) AF: 0.000719 AC: 11 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5180

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000829 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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Maturity-onset diabetes of the young type 7 (2)
-	-	1	Monogenic diabetes (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.19	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.45
MVP		0.87
MPC		0.023
ClinPred		0.017	T
GERP RS		1.4
Varity_R		0.073
gMVP		0.14
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs150096859; hg19: chr2-10186320; COSMIC: COSV109421629;