11-65712316-G-T

Position:

• chr11-65712316-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_182710.3(KAT5):​c.49G>T​(p.Gly17Trp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KAT5 NM_182710.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

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 2 ACMG points.

• 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=0.38764235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT5	NM_182710.3	c.49G>T	p.Gly17Trp	missense_variant	1/13	ENST00000341318.9	NP_874369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT5	ENST00000341318.9	c.49G>T	p.Gly17Trp	missense_variant	1/13	1	NM_182710.3	ENSP00000340330

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

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

Feb 28, 2023

The c.49G>T (p.G17W) alteration is located in exon 1 (coding exon 1) of the KAT5 gene. This alteration results from a G to T substitution at nucleotide position 49, causing the glycine (G) at amino acid position 17 to be replaced by a tryptophan (W). 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
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	32
DANN	Uncertain	0.98
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.78	T;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.37	T
MutationTaster	Benign	0.72	D;D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.028	D;D
Polyphen		1.0	D;.
Vest4		0.35
MutPred		0.27		Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);
MVP		0.74
MPC		2.1
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
gMVP		0.50

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

Other links and lift over

dbSNP: rs992030146; hg19: chr11-65479787;