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GeneBe

3-20072399-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003884.5(KAT2B):c.370G>C(p.Asp124His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KAT2B
NM_003884.5 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.98
Variant links:
Genes affected
KAT2B (HGNC:8638): (lysine acetyltransferase 2B) CBP and p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including c-jun and the adenoviral oncoprotein E1A. The protein encoded by this gene associates with p300/CBP. It has in vitro and in vivo binding activity with CBP and p300, and competes with E1A for binding sites in p300/CBP. It has histone acetyl transferase activity with core histones and nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KAT2BNM_003884.5 linkuse as main transcriptc.370G>C p.Asp124His missense_variant 2/18 ENST00000263754.5
KAT2BXM_005265528.5 linkuse as main transcriptc.370G>C p.Asp124His missense_variant 2/17
KAT2BXM_047449147.1 linkuse as main transcriptc.79G>C p.Asp27His missense_variant 4/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KAT2BENST00000263754.5 linkuse as main transcriptc.370G>C p.Asp124His missense_variant 2/181 NM_003884.5 P1
KAT2BENST00000426228.1 linkuse as main transcriptn.150G>C non_coding_transcript_exon_variant 2/54

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251248
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135770
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:
6.84e-7
AC:
1
AN:
1461216
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726982
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

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 GeneticsAug 04, 2023The c.370G>C (p.D124H) alteration is located in exon 2 (coding exon 2) of the KAT2B gene. This alteration results from a G to C substitution at nucleotide position 370, causing the aspartic acid (D) at amino acid position 124 to be replaced by a histidine (H). 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
Pathogenic
0.71
BayesDel_addAF
Benign
-0.061
T
BayesDel_noAF
Benign
-0.33
Cadd
Pathogenic
27
Dann
Uncertain
0.99
DEOGEN2
Pathogenic
0.80
D
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.035
D
MetaRNN
Pathogenic
0.85
D
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-4.1
D
REVEL
Uncertain
0.44
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.0070
D
Polyphen
1.0
D
Vest4
0.50
MutPred
0.79
Loss of helix (P = 0.0376);
MVP
0.20
MPC
1.4
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.48
gMVP
0.61

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: rs749538432; hg19: chr3-20113891; API