3-126352198-G-T

Variant summary

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

The ENST00000296233.4(KLF15):​c.725C>A​(p.Ala242Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000488 in 1,557,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A242T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

KLF15
ENST00000296233.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38
Variant links:
Genes affected
KLF15 (HGNC:14536): (KLF transcription factor 15) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of peptidyl-lysine acetylation and positive regulation of transcription by RNA polymerase II. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.13639975).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLF15NM_014079.4 linkuse as main transcriptc.725C>A p.Ala242Asp missense_variant 2/3 ENST00000296233.4 NP_054798.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLF15ENST00000296233.4 linkuse as main transcriptc.725C>A p.Ala242Asp missense_variant 2/31 NM_014079.4 ENSP00000296233 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000216
AC:
4
AN:
185442
Hom.:
0
AF XY:
0.0000204
AC XY:
2
AN XY:
98206
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:
0.0000469
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000527
AC:
74
AN:
1405290
Hom.:
0
Cov.:
32
AF XY:
0.0000490
AC XY:
34
AN XY:
693382
show subpopulations
Gnomad4 AFR exome
AF:
0.0000313
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:
0.0000663
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000716
Hom.:
0
Bravo
AF:
0.0000113

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 GeneticsDec 12, 2023The c.725C>A (p.A242D) alteration is located in exon 2 (coding exon 1) of the KLF15 gene. This alteration results from a C to A substitution at nucleotide position 725, causing the alanine (A) at amino acid position 242 to be replaced by an aspartic acid (D). 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
0.23
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.18
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
0.62
D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.34
N
REVEL
Benign
0.070
Sift
Benign
0.051
T
Sift4G
Benign
0.33
T
Polyphen
0.11
B
Vest4
0.32
MutPred
0.32
Loss of glycosylation at P239 (P = 0.0274);
MVP
0.20
MPC
0.39
ClinPred
0.29
T
GERP RS
4.4
Varity_R
0.11
gMVP
0.47

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: rs961177388; hg19: chr3-126071041; API