8-41932252-C-T

Variant names:

• chr8-41932252-C-T
• rs1159509176
• NM_006766.5:c.5968G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006766.5(KAT6A):​c.5968G>A​(p.Ala1990Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KAT6A NM_006766.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

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]

KAT6A Gene-Disease associations (from GenCC):

• autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Illumina
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10052827).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006766.5. 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
	KAT6A	NM_006766.5	MANE Select	c.5968G>A	p.Ala1990Thr	missense	Exon 17 of 17	NP_006757.2	Q92794

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT6A	ENST00000265713.8	TSL:1 MANE Select	c.5968G>A	p.Ala1990Thr	missense	Exon 17 of 17	ENSP00000265713.2	Q92794
	KAT6A	ENST00000406337.6	TSL:5	c.5974G>A	p.Ala1992Thr	missense	Exon 18 of 18	ENSP00000385888.2	A0A3F2YNX6
	KAT6A	ENST00000396930.4	TSL:5	c.5968G>A	p.Ala1990Thr	missense	Exon 18 of 18	ENSP00000380136.3	Q92794

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250132 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461026 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726800

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111572

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.092
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		3.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.13	B
Vest4		0.55
MutPred		0.13		Gain of glycosylation at A1990 (P = 0.0075)
MVP		0.65
MPC		0.18
ClinPred		0.27	T
GERP RS		5.9
Varity_R		0.057
gMVP		0.67
Mutation Taster		=77/22	polymorphism

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

Other links and lift over

dbSNP: rs1159509176; hg19: chr8-41789770;