11-65713695-T-C

Variant names:

• chr11-65713695-T-C
• rs1151500
• NM_182710.3:c.615+28T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182710.3(KAT5):​c.615+28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 1,613,820 control chromosomes in the GnomAD database, including 648,203 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 0.86 (56950 hom., cov: 31)
  • Exomes 𝑓: 0.90 (591253 hom.)
• Consequence: KAT5 NM_182710.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 21 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT5	NM_182710.3	MANE Select	c.615+28T>C		intron	N/A	NP_874369.1
	KAT5	NM_006388.4		c.516+28T>C		intron	N/A	NP_006379.2
	KAT5	NM_001206833.2		c.459+28T>C		intron	N/A	NP_001193762.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT5	ENST00000341318.9	TSL:1 MANE Select	c.615+28T>C		intron	N/A	ENSP00000340330.4
	KAT5	ENST00000377046.7	TSL:1	c.516+28T>C		intron	N/A	ENSP00000366245.3
	KAT5	ENST00000530446.5	TSL:1	c.459+28T>C		intron	N/A	ENSP00000434765.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131186 AN: 152094 Hom.: 56911 Cov.: 31

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.871

GnomAD2 exomes AF: 0.870 AC: 218784 AN: 251376 AF XY: 0.867

Gnomad AFR exome AF: 0.765

Gnomad AMR exome AF: 0.864

Gnomad ASJ exome AF: 0.885

Gnomad EAS exome AF: 0.897

Gnomad FIN exome AF: 0.903

Gnomad NFE exome AF: 0.915

Gnomad OTH exome AF: 0.894

GnomAD4 exome AF: 0.898 AC: 1312306 AN: 1461608 Hom.: 591253 Cov.: 42 AF XY: 0.894 AC XY: 649874 AN XY: 727132

African (AFR) AF: 0.766 AC: 25643 AN: 33478

American (AMR) AF: 0.866 AC: 38722 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 23103 AN: 26130

East Asian (EAS) AF: 0.894 AC: 35476 AN: 39700

South Asian (SAS) AF: 0.728 AC: 62794 AN: 86246

European-Finnish (FIN) AF: 0.903 AC: 48259 AN: 53416

Middle Eastern (MID) AF: 0.891 AC: 5142 AN: 5768

European-Non Finnish (NFE) AF: 0.917 AC: 1019432 AN: 1111764

Other (OTH) AF: 0.890 AC: 53735 AN: 60386

GnomAD4 genome AF: 0.863 AC: 131286 AN: 152212 Hom.: 56950 Cov.: 31 AF XY: 0.861 AC XY: 64060 AN XY: 74430

African (AFR) AF: 0.772 AC: 32026 AN: 41510

American (AMR) AF: 0.871 AC: 13321 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3109 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4620 AN: 5170

South Asian (SAS) AF: 0.721 AC: 3477 AN: 4824

European-Finnish (FIN) AF: 0.902 AC: 9574 AN: 10612

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62299 AN: 68012

Other (OTH) AF: 0.869 AC: 1834 AN: 2110

Alfa AF: 0.897 Hom.: 114451

Bravo AF: 0.859

Asia WGS AF: 0.793 AC: 2759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.27
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1151500; hg19: chr11-65481166;