11-65714532-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_182710.3(KAT5):c.728C>T(p.Pro243Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.51

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]

RNASEH2C (HGNC:24116): (ribonuclease H2 subunit C) This gene encodes a ribonuclease H subunit that can cleave ribonucleotides from RNA:DNA duplexes. Mutations in this gene cause Aicardi-Goutieres syndrome-3, a disease that causes severe neurologic dysfunction. A pseudogene for this gene has been identified on chromosome Y, near the sex determining region Y (SRY) gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, KAT5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT5	NM_182710.3	c.728C>T	p.Pro243Leu	missense_variant	7/13	ENST00000341318.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT5	ENST00000341318.9	c.728C>T	p.Pro243Leu	missense_variant	7/13	1	NM_182710.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 19, 2024

The c.728C>T (p.P243L) alteration is located in exon 7 (coding exon 7) of the KAT5 gene. This alteration results from a C to T substitution at nucleotide position 728, causing the proline (P) at amino acid position 243 to be replaced by a leucine (L). 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	0.93
BayesDel_addAF	Benign	0.0065	T
BayesDel_noAF	Benign	-0.23
Cadd	Pathogenic	28
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;.;.;.;.;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.52	D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.8	D;D;D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.11	T;T;T;T;T;D
Sift4G	Benign	0.084	T;T;T;T;T;T
Polyphen		0.39	B;P;P;.;.;.
Vest4		0.78
MutPred		0.29		Loss of loop (P = 0.0288);.;.;.;.;.;
MVP		0.54
MPC		1.6
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.33
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-65482003;