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GeneBe

13-73846133-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000377669.7(KLF12):c.364C>T(p.Arg122Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000651 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

KLF12
ENST00000377669.7 missense

Scores

4
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89
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 -4 ACMG points.

BS2
High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KLF12NM_001400136.1 linkuse as main transcriptc.364C>T p.Arg122Cys missense_variant 4/8 ENST00000703967.1
KLF12NM_001400153.1 linkuse as main transcriptc.364C>T p.Arg122Cys missense_variant 4/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KLF12ENST00000703967.1 linkuse as main transcriptc.364C>T p.Arg122Cys missense_variant 4/8 NM_001400136.1 P1Q9Y4X4-1
KLF12ENST00000377669.7 linkuse as main transcriptc.364C>T p.Arg122Cys missense_variant 4/81 P1Q9Y4X4-1
KLF12ENST00000472022.1 linkuse as main transcriptn.398C>T non_coding_transcript_exon_variant 3/45

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251178
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000623
AC:
91
AN:
1461812
Hom.:
0
Cov.:
32
AF XY:
0.0000591
AC XY:
43
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000737
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152270
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000141
Hom.:
0
Bravo
AF:
0.000128
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 GeneticsMar 07, 2023The c.364C>T (p.R122C) alteration is located in exon 4 (coding exon 3) of the KLF12 gene. This alteration results from a C to T substitution at nucleotide position 364, causing the arginine (R) at amino acid position 122 to be replaced by a cysteine (C). 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
0.26
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Benign
-0.16
Cadd
Pathogenic
33
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.020
T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.58
N
REVEL
Benign
0.16
Sift
Benign
0.049
D
Sift4G
Uncertain
0.055
T
Polyphen
0.98
D
Vest4
0.70
MVP
0.41
MPC
0.55
ClinPred
0.35
T
GERP RS
6.0
Varity_R
0.053
gMVP
0.41

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: rs142451819; hg19: chr13-74420270; API