rs148123124

Variant names:

• chr2-10048119-C-T
• rs148123124
• NM_003597.5:c.782C>T
• KLF11 p.Pro261Leu

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.782C>T​(p.Pro261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,614,198 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (16 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.93
• Publications: 8 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=0.00955826).
• BP6: Variant 2-10048119-C-T is Benign according to our data. Variant chr2-10048119-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 330631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 248 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.782C>T	p.Pro261Leu	missense	Exon 3 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.731C>T	p.Pro244Leu	missense	Exon 3 of 4	NP_001171187.1	O14901-2
	KLF11	NM_001177718.2		c.731C>T	p.Pro244Leu	missense	Exon 3 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.782C>T	p.Pro261Leu	missense	Exon 3 of 4	ENSP00000307023.1	O14901-1
	KLF11	ENST00000535335.1	TSL:2	c.731C>T	p.Pro244Leu	missense	Exon 3 of 4	ENSP00000442722.1	O14901-2
	KLF11	ENST00000540845.5	TSL:2	c.731C>T	p.Pro244Leu	missense	Exon 3 of 4	ENSP00000444690.1	O14901-2

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00249 AC: 627 AN: 251486 AF XY: 0.00246

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00573

Gnomad NFE exome AF: 0.00364

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00215 AC: 3146 AN: 1461882 Hom.: 16 Cov.: 37 AF XY: 0.00219 AC XY: 1595 AN XY: 727242

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00294 AC: 254 AN: 86258

European-Finnish (FIN) AF: 0.00603 AC: 322 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00221 AC: 2458 AN: 1112004

Other (OTH) AF: 0.00157 AC: 95 AN: 60396

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152316 Hom.: 0 Cov.: 33 AF XY: 0.00165 AC XY: 123 AN XY: 74492

African (AFR) AF: 0.000241 AC: 10 AN: 41558

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.00509 AC: 54 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00254 AC: 173 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00227 Hom.: 5

Bravo AF: 0.00108

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00224

EpiControl AF: 0.00243

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.9
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.15
Sift	Benign	0.18	T
Sift4G	Benign	0.096	T
Varity_R		0.22
gMVP		0.44
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs148123124;

hg19: chr2-10188246;