3-126343750-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014079.4(KLF15):c.1228C>T(p.Arg410Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,611,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
KLF15
NM_014079.4 missense
NM_014079.4 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 3.70
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLF15 | NM_014079.4 | c.1228C>T | p.Arg410Cys | missense_variant | 3/3 | ENST00000296233.4 | NP_054798.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KLF15 | ENST00000296233.4 | c.1228C>T | p.Arg410Cys | missense_variant | 3/3 | 1 | NM_014079.4 | ENSP00000296233 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000281 AC: 7AN: 248948Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135034
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GnomAD4 exome AF: 0.0000452 AC: 66AN: 1459482Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 726078
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152360Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74512
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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 submitter | clinical testing | Ambry Genetics | May 26, 2022 | The c.1228C>T (p.R410C) alteration is located in exon 3 (coding exon 2) of the KLF15 gene. This alteration results from a C to T substitution at nucleotide position 1228, causing the arginine (R) at amino acid position 410 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at