Variant 16-31120347-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_ModeratePP5_Moderate

The NM_032188.3(KAT8):c.295C>T(p.Arg99Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R99Q) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

KAT8
NM_032188.3 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.40

Variant links:

Genes affected

KAT8 (HGNC:17933): (lysine acetyltransferase 8) This gene encodes a member of the MYST histone acetylase protein family. The encoded protein has a characteristic MYST domain containing an acetyl-CoA-binding site, a chromodomain typical of proteins which bind histones, and a C2HC-type zinc finger. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

KAT8 links:

KAT8 (HGNC:):

KAT8 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.894

PP5

Variant 16-31120347-C-T is Pathogenic according to our data. Variant chr16-31120347-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 3253327.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT8	NM_032188.3 linkuse as main transcript	c.295C>T	p.Arg99Trp	missense_variant	3/11	ENST00000219797.9	NP_115564.2	Q9H7Z6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KAT8	ENST00000219797.9 linkuse as main transcript	c.295C>T	p.Arg99Trp	missense_variant	3/11	1	NM_032188.3	ENSP00000219797.3	Q9H7Z6-1
KAT8	ENST00000448516.6 linkuse as main transcript	c.295C>T	p.Arg99Trp	missense_variant	3/10	1		ENSP00000406037.2	Q9H7Z6-2
KAT8	ENST00000543774.6 linkuse as main transcript	c.295C>T	p.Arg99Trp	missense_variant	4/12	5		ENSP00000456933.2	Q9H7Z6-1
KAT8	ENST00000539683.2 linkuse as main transcript	n.280C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2024

Published functional studies demonstrate a damaging effect on acetylation activity (PMID: 38135180); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 38135180) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.71

D;.;D

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

.;D;D

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Uncertain

0.20

MutationAssessor

Pathogenic

3.7

H;H;H

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-7.7

.;D;D

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

.;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.82

MutPred

0.70

Loss of MoRF binding (P = 0.0899);Loss of MoRF binding (P = 0.0899);Loss of MoRF binding (P = 0.0899);

MVP

0.81

MPC

2.3

ClinPred

1.0

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.88

gMVP

0.95

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.

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