2-10047878-G-C

Variant names:

• chr2-10047878-G-C
• rs146238335
• NM_003597.5:c.541G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003597.5(KLF11):​c.541G>C​(p.Glu181Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.16

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09810236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5	c.541G>C	p.Glu181Gln	missense_variant	Exon 3 of 4	ENST00000305883.6	NP_003588.1
KLF11	NM_001177716.2	c.490G>C	p.Glu164Gln	missense_variant	Exon 3 of 4		NP_001171187.1
KLF11	NM_001177718.2	c.490G>C	p.Glu164Gln	missense_variant	Exon 3 of 4		NP_001171189.1
KLF11	XM_047446025.1	c.490G>C	p.Glu164Gln	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.541G>C	p.Glu181Gln	missense_variant	Exon 3 of 4	1	NM_003597.5	ENSP00000307023.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251036 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135694

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 6.84e-7 AC: 1 AN: 1461506 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 727054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T;.;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.65	T;T;.
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.094
Sift	Benign	0.040	D;D;D
Sift4G	Benign	0.070	T;T;T
Polyphen		0.0060	B;.;.
Vest4		0.12
MutPred		0.26		Gain of MoRF binding (P = 0.0678);.;.;
MVP		0.48
MPC		0.021
ClinPred		0.22	T
GERP RS		3.0
Varity_R		0.12
gMVP		0.21

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: rs146238335; hg19: chr2-10188005;