11-65713618-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate
The NM_182710.3(KAT5):c.566C>T(p.Pro189Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,078 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: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
KAT5
NM_182710.3 missense
NM_182710.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.66
Genes affected
KAT5 (HGNC:5275): (lysine acetyltransferase 5) The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was originally isolated as an HIV-1 TAT-interactive protein. HATs play important roles in regulating chromatin remodeling, transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
?
In a mutagenesis_site In K6R; abolished autoacetylation; when associated with R-104, R-120, R-148, R-150 and R-187. (size 0) in uniprot entity KAT5_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, KAT5
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21912012).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KAT5 | NM_182710.3 | c.566C>T | p.Pro189Leu | missense_variant | 5/13 | ENST00000341318.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KAT5 | ENST00000341318.9 | c.566C>T | p.Pro189Leu | missense_variant | 5/13 | 1 | NM_182710.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
4
AN:
152188
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461890Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0AN XY: 727246
GnomAD4 exome
AF:
AC:
1
AN:
1461890
Hom.:
Cov.:
43
AF XY:
AC XY:
0
AN XY:
727246
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74328
GnomAD4 genome
?
AF:
AC:
4
AN:
152188
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74328
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
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 | Aug 02, 2021 | The c.566C>T (p.P189L) alteration is located in exon 5 (coding exon 5) of the KAT5 gene. This alteration results from a C to T substitution at nucleotide position 566, causing the proline (P) at amino acid position 189 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;D;T
Sift4G
Benign
T;T;D;D;T;T
Polyphen
P;B;P;.;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0677);.;.;.;.;.;
MVP
MPC
1.1
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at