11-65713412-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1 PM2 PP2 BP4_Moderate

The NM_182710.3(KAT5):c.449A>C(p.Asn150Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KAT5 NM_182710.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue N6-acetyllysine; by autocatalysis (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=0.14118642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT5	NM_182710.3	c.449A>C	p.Asn150Thr	missense_variant	4/13	ENST00000341318.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT5	ENST00000341318.9	c.449A>C	p.Asn150Thr	missense_variant	4/13	1	NM_182710.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

The c.449A>C (p.N150T) alteration is located in exon 4 (coding exon 4) of the KAT5 gene. This alteration results from a A to C substitution at nucleotide position 449, causing the asparagine (N) at amino acid position 150 to be replaced by a threonine (T). 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	0.086
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	21
Dann	Benign	0.92
DEOGEN2	Benign	0.15	T;.;T
Eigen	Benign	-0.091
Eigen_PC	Benign	-0.0044
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.23	N;N;N
REVEL	Benign	0.077
Sift	Benign	0.58	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.049	B;B;.
Vest4		0.37
MutPred		0.16		Gain of phosphorylation at N117 (P = 0.0305);.;.;
MVP		0.74
MPC		0.85
ClinPred		0.15	T
GERP RS		3.2
Varity_R		0.063
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65480883;