2-10046292-A-T

Position:

• chr2-10046292-A-T

Variant summary

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

The NM_003597.5(KLF11):​c.185A>T​(p.Gln62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. Q62R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09

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=0.20418054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF11	NM_003597.5	c.185A>T	p.Gln62Leu	missense_variant	2/4	ENST00000305883.6
KLF11	NM_001177716.2	c.134A>T	p.Gln45Leu	missense_variant	2/4
KLF11	NM_001177718.2	c.134A>T	p.Gln45Leu	missense_variant	2/4
KLF11	XM_047446025.1	c.134A>T	p.Gln45Leu	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF11	ENST00000305883.6	c.185A>T	p.Gln62Leu	missense_variant	2/4	1	NM_003597.5	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T;D;.;.;T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.54	T;T;T;T;T;.
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	0.81	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.1	D;D;D;D;D;D
REVEL	Benign	0.087
Sift	Benign	0.051	T;D;D;D;T;D
Sift4G	Uncertain	0.046	D;T;T;T;D;T
Polyphen		0.45	.;P;.;.;.;.
Vest4		0.51, 0.49, 0.49
MutPred		0.22		.;Loss of methylation at K63 (P = 0.0481);.;.;.;.;
MVP		0.84
MPC		0.067
ClinPred		0.59	D
GERP RS		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.15

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: rs35927125; hg19: chr2-10186419;