chr2-207124179-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003709.4(KLF7):​c.328C>T​(p.Leu110Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KLF7
NM_003709.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41
Variant links:
Genes affected
KLF7 (HGNC:6350): (KLF transcription factor 7) The protein encoded by this gene is a member of the Kruppel-like transcriptional regulator family. Members in this family regulate cell proliferation, differentiation and survival and contain three C2H2 zinc fingers at the C-terminus that mediate binding to GC-rich sites. This protein may contribute to the progression of type 2 diabetes by inhibiting insulin expression and secretion in pancreatic beta-cells and by deregulating adipocytokine secretion in adipocytes. A pseudogene of this gene is located on the long arm of chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

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ACMG classification

Classification made for transcript

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=0.14026627).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLF7NM_003709.4 linkuse as main transcriptc.328C>T p.Leu110Phe missense_variant 2/4 ENST00000309446.11 NP_003700.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLF7ENST00000309446.11 linkuse as main transcriptc.328C>T p.Leu110Phe missense_variant 2/41 NM_003709.4 ENSP00000309570 P1O75840-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 18, 2022The c.328C>T (p.L110F) alteration is located in exon 2 (coding exon 2) of the KLF7 gene. This alteration results from a C to T substitution at nucleotide position 328, causing the leucine (L) at amino acid position 110 to be replaced by a phenylalanine (F). 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
Uncertain
0.35
BayesDel_addAF
Benign
-0.095
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
.;T;.;.;.;.
Eigen
Benign
0.042
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.82
T;T;T;T;T;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.14
T;T;T;T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
0.41
.;N;.;N;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.63
N;N;N;N;N;N
REVEL
Benign
0.10
Sift
Benign
0.84
T;T;T;T;T;D
Sift4G
Benign
0.72
T;T;T;T;T;.
Polyphen
0.87
.;P;.;.;.;.
Vest4
0.24
MutPred
0.33
.;Loss of disorder (P = 0.0669);.;Loss of disorder (P = 0.0669);.;Loss of disorder (P = 0.0669);
MVP
0.17
MPC
0.37
ClinPred
0.47
T
GERP RS
5.9
Varity_R
0.16
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-207988903; API