rs548231613

Positions:

• chr8-41933168-CTGCGGCTGCTGT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4 BP6_Very_Strong BS2

The NM_006766.5(KAT6A):​c.5040_5051del​(p.Gln1681_Gln1684del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00129 in 1,597,142 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00094 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (5 hom.)
• Consequence: KAT6A NM_006766.5 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.99

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 -10 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006766.5.
• BP6: Variant 8-41933168-CTGCGGCTGCTGT-C is Benign according to our data. Variant chr8-41933168-CTGCGGCTGCTGT-C is described in ClinVar as [Likely_benign]. Clinvar id is 589281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6A	NM_006766.5	c.5040_5051del	p.Gln1681_Gln1684del	inframe_deletion	17/17	ENST00000265713.8	NP_006757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6A	ENST00000265713.8	c.5040_5051del	p.Gln1681_Gln1684del	inframe_deletion	17/17	1	NM_006766.5	ENSP00000265713	A2

Frequencies

GnomAD3 genomes AF: 0.000942 AC: 143 AN: 151738 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00177

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000884 AC: 196 AN: 221694 Hom.: 1 AF XY: 0.000801 AC XY: 96 AN XY: 119818

Gnomad AFR exome AF: 0.0000728

Gnomad AMR exome AF: 0.000931

Gnomad ASJ exome AF: 0.000212

Gnomad EAS exome AF: 0.000709

Gnomad SAS exome AF: 0.0000349

Gnomad FIN exome AF: 0.000300

Gnomad NFE exome AF: 0.00138

Gnomad OTH exome AF: 0.00162

GnomAD4 exome AF: 0.00133 AC: 1918 AN: 1445286 Hom.: 5 AF XY: 0.00128 AC XY: 917 AN XY: 717976

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000991

Gnomad4 ASJ exome AF: 0.000271

Gnomad4 EAS exome AF: 0.000254

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.000375

Gnomad4 NFE exome AF: 0.00159

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.000942 AC: 143 AN: 151856 Hom.: 0 Cov.: 31 AF XY: 0.00104 AC XY: 77 AN XY: 74220

Gnomad4 AFR AF: 0.0000967

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00177

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.000941

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	KAT6A: BS1 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 20, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 30, 2018

- -

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2018

This alteration is classified as 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs548231613; hg19: chr8-41790686;