rs145933214

Variant names:

• chr2-10047747-A-C
• rs145933214
• NM_003597.5:c.410A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-10047747-A-C
• chr2-10047747-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003597.5(KLF11):​c.410A>C​(p.Asp137Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D137G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 5 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: 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=0.028356075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5	c.410A>C	p.Asp137Ala	missense_variant	Exon 3 of 4	ENST00000305883.6	NP_003588.1
KLF11	NM_001177716.2	c.359A>C	p.Asp120Ala	missense_variant	Exon 3 of 4		NP_001171187.1
KLF11	NM_001177718.2	c.359A>C	p.Asp120Ala	missense_variant	Exon 3 of 4		NP_001171189.1
KLF11	XM_047446025.1	c.359A>C	p.Asp120Ala	missense_variant	Exon 3 of 4		XP_047301981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6	c.410A>C	p.Asp137Ala	missense_variant	Exon 3 of 4	1	NM_003597.5	ENSP00000307023.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152114 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461488 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 727080

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152114 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.63
DANN	Benign	0.20
DEOGEN2	Benign	0.050	T;T;.;.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.32	T;T;T;T;T;.
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.028	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.2	.;N;.;.;.;.
PhyloP100		1.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.2	N;N;N;N;N;N
REVEL	Benign	0.090
Sift	Benign	0.49	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0	.;B;.;.;.;.
Vest4		0.040, 0.045
MutPred		0.19		.;Gain of glycosylation at T134 (P = 0.0487);.;.;.;.;
MVP		0.39
MPC		0.022
ClinPred		0.034	T
GERP RS		3.1
Varity_R		0.039
gMVP		0.15
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145933214; hg19: chr2-10187874;