chr2-10047804-G-T

Variant names:

• chr2-10047804-G-T
• rs587780378
• NM_003597.5:c.467G>T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_003597.5(KLF11):​c.467G>T​(p.Gly156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000027 (1 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 0.331

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022491246).
• BP6: Variant 2-10047804-G-T is Benign according to our data. Variant chr2-10047804-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 129432.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
• BS2: High AC in GnomAdExome4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5	c.467G>T	p.Gly156Val	missense_variant	Exon 3 of 4	ENST00000305883.6	NP_003588.1
KLF11	NM_001177716.2	c.416G>T	p.Gly139Val	missense_variant	Exon 3 of 4		NP_001171187.1
KLF11	NM_001177718.2	c.416G>T	p.Gly139Val	missense_variant	Exon 3 of 4		NP_001171189.1
KLF11	XM_047446025.1	c.416G>T	p.Gly139Val	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.467G>T	p.Gly156Val	missense_variant	Exon 3 of 4	1	NM_003597.5	ENSP00000307023.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000143 AC: 36 AN: 251052 Hom.: 1 AF XY: 0.000125 AC XY: 17 AN XY: 135720

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00101

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: 0.000163

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1461372 Hom.: 1 Cov.: 37 AF XY: 0.0000275 AC XY: 20 AN XY: 726988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000850

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000869

ExAC AF: 0.000115 AC: 14

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Jun 27, 2013

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Uncertain:1

Oct 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.467G>T (p.G156V) alteration is located in exon 3 (coding exon 3) of the KLF11 gene. This alteration results from a G to T substitution at nucleotide position 467, causing the glycine (G) at amino acid position 156 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.35
DANN	Benign	0.57
DEOGEN2	Benign	0.20	T;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.49	T;T;T;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.022	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.067
Sift	Benign	0.11	T;T;T;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.012	B;.;.;.
Vest4		0.13
MutPred		0.30		Loss of methylation at R155 (P = 0.0554);.;.;.;
MVP		0.57
MPC		0.023
ClinPred		0.033	T
GERP RS		-0.96
Varity_R		0.053
gMVP		0.35

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: rs587780378; hg19: chr2-10187931;