Variant 11-65713412-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11

Variant links:

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]

KAT5 links:

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ACMG classification

Classification made for transcript

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 in gene, where missense usually causes diseases (based on misZ statistic), KAT5. . Gene score misZ 3.6126 (greater than the threshold 3.09). Trascript score misZ 3.7394 (greater than threshold 3.09). GenCC has associacion of gene with neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities.

BP4

Computational evidence support a benign effect (MetaRNN=0.14118642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT5	NM_182710.3 linkuse as main transcript	c.449A>C	p.Asn150Thr	missense_variant	4/13	ENST00000341318.9	NP_874369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT5	ENST00000341318.9 linkuse as main transcript	c.449A>C	p.Asn150Thr	missense_variant	4/13	1	NM_182710.3	ENSP00000340330		Q92993-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

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

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.15

T;.;T

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.0044

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.0051

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

D;D;D;N;N

PrimateAI

Uncertain

0.67

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over