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GeneBe

13-73813270-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The ENST00000377669.7(KLF12):c.688G>A(p.Gly230Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

KLF12
ENST00000377669.7 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.39
Variant links:
Genes affected
KLF12 (HGNC:6346): (KLF transcription factor 12) Activator protein-2 alpha (AP-2 alpha) is a developmentally-regulated transcription factor and important regulator of gene expression during vertebrate development and carcinogenesis. The protein encoded by this gene is a member of the Kruppel-like zinc finger protein family and can repress expression of the AP-2 alpha gene by binding to a specific site in the AP-2 alpha gene promoter. Repression by the encoded protein requires binding with a corepressor, CtBP1. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.40537286).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KLF12NM_001400136.1 linkuse as main transcriptc.688G>A p.Gly230Ser missense_variant 5/8 ENST00000703967.1
KLF12NM_001400153.1 linkuse as main transcriptc.688G>A p.Gly230Ser missense_variant 5/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KLF12ENST00000703967.1 linkuse as main transcriptc.688G>A p.Gly230Ser missense_variant 5/8 NM_001400136.1 P1Q9Y4X4-1
KLF12ENST00000377669.7 linkuse as main transcriptc.688G>A p.Gly230Ser missense_variant 5/81 P1Q9Y4X4-1
KLF12ENST00000472022.1 linkuse as main transcriptn.722G>A non_coding_transcript_exon_variant 4/45

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251118
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135706
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461720
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727168
show subpopulations
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:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000756
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 26, 2022The c.688G>A (p.G230S) alteration is located in exon 5 (coding exon 4) of the KLF12 gene. This alteration results from a G to A substitution at nucleotide position 688, causing the glycine (G) at amino acid position 230 to be replaced by a serine (S). 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
0.24
BayesDel_addAF
Benign
-0.012
T
BayesDel_noAF
Benign
-0.25
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Benign
0.011
T
Eigen
Benign
0.053
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.41
T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
0.53
N
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
0.49
N
REVEL
Uncertain
0.32
Sift
Benign
0.60
T
Sift4G
Benign
0.95
T
Polyphen
0.54
P
Vest4
0.80
MutPred
0.29
Loss of loop (P = 0.0128);
MVP
0.17
MPC
0.43
ClinPred
0.79
D
GERP RS
5.5
Varity_R
0.22
gMVP
0.48

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1462483269; hg19: chr13-74387407; API