2-10043739-G-T

Variant names:

• chr2-10043739-G-T
• NM_003597.5:c.23G>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.23G>T​(p.Gly8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 1,233,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671

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=0.20145991).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5	c.23G>T	p.Gly8Val	missense_variant	Exon 1 of 4	ENST00000305883.6	NP_003588.1
KLF11	NM_001177716.2	c.-158G>T		upstream_gene_variant			NP_001171187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6	c.23G>T	p.Gly8Val	missense_variant	Exon 1 of 4	1	NM_003597.5	ENSP00000307023.1
KLF11	ENST00000401510.5	c.-10+668G>T		intron_variant	Intron 1 of 2	3		ENSP00000386058.1
KLF11	ENST00000540845.5	c.-158G>T		upstream_gene_variant		2		ENSP00000444690.1
KLF11	ENST00000448523.5	c.-158G>T		upstream_gene_variant		4		ENSP00000387866.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000162 AC: 2 AN: 1233506 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 608878

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000456

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.066
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.037	D
Polyphen		0.65	P
Vest4		0.22
MutPred		0.089		Loss of disorder (P = 0.128);
MVP		0.60
MPC		0.19
ClinPred		0.51	D
GERP RS		2.5
Varity_R		0.061
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-10183866;