Genetic Variant KAT8:c.463-644C>T (chr16-31126391-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032188.3(KAT8):c.463-644C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,518 control chromosomes in the GnomAD database, including 9,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 9685 hom., cov: 32)

Exomes 𝑓: 0.30 ( 31 hom. )

Consequence

KAT8
NM_032188.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.87

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

Li-Ghorbani-Weisz-Hubshman syndrome
Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

KAT8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032188.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT8	NM_032188.3	MANE Select	c.463-644C>T		intron	N/A	NP_115564.2	Q9H7Z6-1
	KAT8	NM_182958.4		c.463-644C>T		intron	N/A	NP_892003.2	Q9H7Z6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KAT8	ENST00000219797.9	TSL:1 MANE Select	c.463-644C>T	intron	N/A	ENSP00000219797.3	Q9H7Z6-1
KAT8	ENST00000448516.6	TSL:1	c.463-644C>T	intron	N/A	ENSP00000406037.2	Q9H7Z6-2
KAT8	ENST00000538768.2	TSL:1	n.808C>T	non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48378

AN:

151886

Hom.:

9682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.436

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.382

GnomAD4 exome

AF:

0.298

AC:

153

AN:

514

Hom.:

Cov.:

AF XY:

0.301

AC XY:

106

AN XY:

352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.389

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.122

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.308

AC:

112

AN:

364

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.318

AC:

48386

AN:

152004

Hom.:

9685

Cov.:

AF XY:

0.321

AC XY:

23866

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.125

AC:

5188

AN:

41462

American (AMR)

AF:

0.380

AC:

5807

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1721

AN:

3470

East Asian (EAS)

AF:

0.891

AC:

4607

AN:

5168

South Asian (SAS)

AF:

0.177

AC:

852

AN:

4818

European-Finnish (FIN)

AF:

0.391

AC:

4128

AN:

10552

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24729

AN:

67952

Other (OTH)

AF:

0.380

AC:

802

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1518

3037

4555

6074

7592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.364

Hom.:

8417

Bravo

AF:

0.322

Asia WGS

AF:

0.463

AC:

1614

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.030

(source)

DANN

Benign

0.47

PhyloP100

-3.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over