2-10043736-C-G

Variant names:

• chr2-10043736-C-G
• NM_003597.5:c.20C>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003597.5(KLF11):​c.20C>G​(p.Ala7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000568 in 1,233,034 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: 0.0000057 (0 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06334147).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5	c.20C>G	p.Ala7Gly	missense_variant	Exon 1 of 4	ENST00000305883.6	NP_003588.1
KLF11	NM_001177716.2	c.-161C>G		upstream_gene_variant			NP_001171187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6	c.20C>G	p.Ala7Gly	missense_variant	Exon 1 of 4	1	NM_003597.5	ENSP00000307023.1
KLF11	ENST00000401510.5	c.-10+665C>G		intron_variant	Intron 1 of 2	3		ENSP00000386058.1
KLF11	ENST00000540845.5	c.-161C>G		upstream_gene_variant		2		ENSP00000444690.1
KLF11	ENST00000448523.5	c.-161C>G		upstream_gene_variant		4		ENSP00000387866.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000568 AC: 7 AN: 1233034 Hom.: 0 Cov.: 29 AF XY: 0.00000986 AC XY: 6 AN XY: 608682

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000710

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.90
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.0050
Sift	Benign	0.30	T
Sift4G	Benign	0.37	T
Polyphen		0.0020	B
Vest4		0.056
MutPred		0.13		Loss of stability (P = 0.1496);
MVP		0.29
MPC		0.021
ClinPred		0.030	T
GERP RS		-0.72
Varity_R		0.045
gMVP		0.12

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: chr2-10183863;