Variant chr16-31120249-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3PP5_Moderate

The ENST00000219797.9(KAT8):c.275A>G(p.His92Arg) 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 (★).

Frequency

Genomes: not found (cov: 33)

Consequence

KAT8
ENST00000219797.9 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 8.37

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 2 uncertain in ENST00000219797.9

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.795

PP5

Variant 16-31120249-A-G is Pathogenic according to our data. Variant chr16-31120249-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 1684624.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.275A>G	p.His92Arg	missense_variant	2/11	ENST00000219797.9	NP_115564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT8	ENST00000219797.9 linkuse as main transcript	c.275A>G	p.His92Arg	missense_variant	2/11	1	NM_032188.3	ENSP00000219797	P1	Q9H7Z6-1
KAT8	ENST00000448516.6 linkuse as main transcript	c.275A>G	p.His92Arg	missense_variant	2/10	1		ENSP00000406037		Q9H7Z6-2
KAT8	ENST00000543774.6 linkuse as main transcript	c.275A>G	p.His92Arg	missense_variant	3/12	5		ENSP00000456933	P1	Q9H7Z6-1
KAT8	ENST00000539683.2 linkuse as main transcript	n.260A>G		non_coding_transcript_exon_variant	2/3	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

Li-Ghorbani-Weisz-Hubshman syndrome

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Laboratory of Medical Genetics, National & Kapodistrian University of Athens

May 23, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

D;.;D

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

1.0

.;D;D

M_CAP

Uncertain

0.096

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Uncertain

0.32

MutationAssessor

Pathogenic

3.0

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-7.7

.;D;D

REVEL

Pathogenic

0.67

Sift

Benign

0.037

.;D;T

Sift4G

Benign

0.063

T;T;T

Polyphen

1.0

D;.;D

Vest4

0.69

MutPred

0.64

Gain of MoRF binding (P = 0.0233);Gain of MoRF binding (P = 0.0233);Gain of MoRF binding (P = 0.0233);

MVP

0.84

MPC

2.4

ClinPred

1.0

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.71

gMVP

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.56

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.56

Position offset: -5

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