rs1553312823

Positions:

• chr2-10043738-G-A
• chr2-10043738-G-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.22G>A​(p.Gly8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000811 in 1,232,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 8.1e-7 (0 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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=0.10102469).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF11	NM_003597.5	c.22G>A	p.Gly8Ser	missense_variant	1/4	ENST00000305883.6	NP_003588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6	c.22G>A	p.Gly8Ser	missense_variant	1/4	1	NM_003597.5	ENSP00000307023	A2
KLF11	ENST00000401510.5	c.-10+667G>A		intron_variant		3		ENSP00000386058

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.11e-7 AC: 1 AN: 1232970 Hom.: 0 Cov.: 29 AF XY: 0.00000164 AC XY: 1 AN XY: 608664

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000135

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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	-0.68
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.034
Sift	Benign	0.15	T
Sift4G	Benign	0.45	T
Polyphen		0.0070	B
Vest4		0.16
MutPred		0.18		Gain of phosphorylation at G8 (P = 0.0267);
MVP		0.38
MPC		0.17
ClinPred		0.24	T
GERP RS		0.46
Varity_R		0.047
gMVP		0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553312823; hg19: chr2-10183865;