rs117270099

Variant names:

• chr8-41932226-G-A
• rs117270099
• NM_006766.5:c.5994C>T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006766.5(KAT6A):​c.5994C>T​(p.Asn1998Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000888 in 1,606,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00086 (0 hom.)
• Consequence: KAT6A NM_006766.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.358

Genes affected

KAT6A (HGNC:13013): (lysine acetyltransferase 6A) This gene encodes a member of the MOZ, YBFR2, SAS2, TIP60 family of histone acetyltransferases. The protein is composed of a nuclear localization domain, a double C2H2 zinc finger domain that binds to acetylated histone tails, a histone acetyl-transferase domain, a glutamate/aspartate-rich region, and a serine- and methionine-rich transactivation domain. It is part of a complex that acetylates lysine-9 residues in histone 3, and in addition, it acts as a co-activator for several transcription factors. Allelic variants of this gene are associated with an autosomal dominant form of cognitive disability. Chromosomal translocations of this gene are associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 8-41932226-G-A is Benign according to our data. Variant chr8-41932226-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 588777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.358 with no splicing effect.
• BS2: High AC in GnomAd4 at 181 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6A	NM_006766.5	c.5994C>T	p.Asn1998Asn	synonymous_variant	Exon 17 of 17	ENST00000265713.8	NP_006757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6A	ENST00000265713.8	c.5994C>T	p.Asn1998Asn	synonymous_variant	Exon 17 of 17	1	NM_006766.5	ENSP00000265713.2
KAT6A	ENST00000406337.6	c.6000C>T	p.Asn2000Asn	synonymous_variant	Exon 18 of 18	5		ENSP00000385888.2
KAT6A	ENST00000396930.4	c.5994C>T	p.Asn1998Asn	synonymous_variant	Exon 18 of 18	5		ENSP00000380136.3
KAT6A	ENST00000649817.1	c.4674C>T	p.Asn1558Asn	synonymous_variant	Exon 11 of 11			ENSP00000497780.1

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000806 AC: 198 AN: 245622 Hom.: 0 AF XY: 0.000738 AC XY: 98 AN XY: 132702

Gnomad AFR exome AF: 0.00265

Gnomad AMR exome AF: 0.000894

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.000202

Gnomad FIN exome AF: 0.0000936

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000857 AC: 1246 AN: 1454094 Hom.: 0 Cov.: 32 AF XY: 0.000819 AC XY: 592 AN XY: 722790

Gnomad4 AFR exome AF: 0.00234

Gnomad4 AMR exome AF: 0.000801

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.000270

Gnomad4 FIN exome AF: 0.000282

Gnomad4 NFE exome AF: 0.000947

Gnomad4 OTH exome AF: 0.000716

GnomAD4 genome AF: 0.00119 AC: 181 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.000995 AC XY: 74 AN XY: 74406

Gnomad4 AFR AF: 0.00253

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.00116

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KAT6A: BP4, BP7 -

Dec 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 27, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Feb 10, 2017

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.9
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs117270099; hg19: chr8-41789744; COSMIC: COSV99705940; COSMIC: COSV99705940;