NM_006766.5:c.5994C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

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.5994C>T	p.Asn1998Asn	synonymous	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.5994C>T	p.Asn1998Asn	synonymous	Exon 17 of 17	ENSP00000265713.2	Q92794
	KAT6A	ENST00000406337.6	TSL:5	c.6000C>T	p.Asn2000Asn	synonymous	Exon 18 of 18	ENSP00000385888.2	A0A3F2YNX6
	KAT6A	ENST00000396930.4	TSL:5	c.5994C>T	p.Asn1998Asn	synonymous	Exon 18 of 18	ENSP00000380136.3	Q92794

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

GnomAD2 exomes AF: 0.000806 AC: 198 AN: 245622 AF XY: 0.000738

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 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

African (AFR) AF: 0.00234 AC: 78 AN: 33268

American (AMR) AF: 0.000801 AC: 35 AN: 43696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25550

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39590

South Asian (SAS) AF: 0.000270 AC: 23 AN: 85214

European-Finnish (FIN) AF: 0.000282 AC: 15 AN: 53240

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5696

European-Non Finnish (NFE) AF: 0.000947 AC: 1049 AN: 1107804

Other (OTH) AF: 0.000716 AC: 43 AN: 60036

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

African (AFR) AF: 0.00253 AC: 105 AN: 41524

American (AMR) AF: 0.000720 AC: 11 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000912 AC: 62 AN: 68014

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.00116

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.9
DANN	Benign	0.62
PhyloP100		0.36
Mutation Taster		=94/6	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: rs117270099; hg19: chr8-41789744; COSMIC: COSV99705940; COSMIC: COSV99705940;