11-65713320-A-G

Variant names:

• chr11-65713320-A-G
• rs551115
• NM_182710.3:c.385-28A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PP3_Moderate BA1

The NM_182710.3(KAT5):​c.385-28A>G variant causes a intron change. The variant allele was found at a frequency of 0.992 in 1,608,002 control chromosomes in the GnomAD database, including 792,136 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.96 (70453 hom., cov: 31)
  • Exomes 𝑓: 1.0 (721683 hom.)
• Consequence: KAT5 NM_182710.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92
• Publications: 10 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT5	NM_182710.3	c.385-28A>G		intron_variant	Intron 3 of 12	ENST00000341318.9	NP_874369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT5	ENST00000341318.9	c.385-28A>G		intron_variant	Intron 3 of 12	1	NM_182710.3	ENSP00000340330.4

Frequencies

GnomAD3 genomes AF: 0.960 AC: 146086 AN: 152182 Hom.: 70398 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.970

GnomAD2 exomes AF: 0.989 AC: 245279 AN: 247886 AF XY: 0.992

Gnomad AFR exome AF: 0.862

Gnomad AMR exome AF: 0.992

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.996 AC: 1449163 AN: 1455702 Hom.: 721683 Cov.: 40 AF XY: 0.996 AC XY: 720242 AN XY: 723068

African (AFR) AF: 0.859 AC: 28636 AN: 33338

American (AMR) AF: 0.991 AC: 43964 AN: 44372

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25976 AN: 25978

East Asian (EAS) AF: 1.00 AC: 39536 AN: 39536

South Asian (SAS) AF: 1.00 AC: 86040 AN: 86074

European-Finnish (FIN) AF: 1.00 AC: 53154 AN: 53176

Middle Eastern (MID) AF: 0.991 AC: 5686 AN: 5740

European-Non Finnish (NFE) AF: 0.999 AC: 1106757 AN: 1107440

Other (OTH) AF: 0.989 AC: 59414 AN: 60048

GnomAD4 genome AF: 0.960 AC: 146200 AN: 152300 Hom.: 70453 Cov.: 31 AF XY: 0.962 AC XY: 71606 AN XY: 74472

African (AFR) AF: 0.865 AC: 35915 AN: 41544

American (AMR) AF: 0.980 AC: 14993 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 1.00 AC: 4825 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10625 AN: 10628

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67948 AN: 68032

Other (OTH) AF: 0.971 AC: 2052 AN: 2114

Alfa AF: 0.982 Hom.: 13460

Bravo AF: 0.954

Asia WGS AF: 0.994 AC: 3454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.87
PhyloP100		3.9
BranchPoint Hunter		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.87		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.87		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs551115; hg19: chr11-65480791;