dbSNP rs1857071943: KAT5:p.Arg86His (chr11-65712931-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PM5PP3PP5

The NM_182710.3(KAT5):c.257G>A(p.Arg86His) 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 (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R86C) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 31)

Consequence

KAT5
NM_182710.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.36

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

KAT5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr11-65712930-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3895531.Status of the report is criteria_provided_single_submitter, 1 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.815

PP5

Variant 11-65712931-G-A is Pathogenic according to our data. Variant chr11-65712931-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 987964.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182710.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KAT5	NM_182710.3	MANE Select	c.257G>A	p.Arg86His	missense	Exon 3 of 13	NP_874369.1	Q92993-3
KAT5	NM_006388.4		c.158G>A	p.Arg53His	missense	Exon 4 of 14	NP_006379.2
KAT5	NM_001206833.2		c.257G>A	p.Arg86His	missense	Exon 3 of 12	NP_001193762.1	Q92993-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KAT5	ENST00000341318.9	TSL:1 MANE Select	c.257G>A	p.Arg86His	missense	Exon 3 of 13	ENSP00000340330.4	Q92993-3
KAT5	ENST00000377046.7	TSL:1	c.158G>A	p.Arg53His	missense	Exon 4 of 14	ENSP00000366245.3	Q92993-1
KAT5	ENST00000530446.5	TSL:1	c.257G>A	p.Arg86His	missense	Exon 3 of 12	ENSP00000434765.1	Q92993-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.69

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.076

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

0.18

MutationAssessor

Pathogenic

3.4

PhyloP100

9.4

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.90

MutPred

0.63

Loss of ubiquitination at K52 (P = 0.0982)

MVP

0.77

MPC

2.1

ClinPred

1.0

GERP RS

4.4

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.81

gMVP

0.97

Mutation Taster

=171/129

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over