rs747034971

Variant names:

• chr8-41934352-GCTC-G
• rs747034971
• NM_006766.5:c.3865_3867delGAG

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PM4_Supporting BP6_Very_Strong BS2

The NM_006766.5(KAT6A):​c.3865_3867delGAG​(p.Glu1289del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: KAT6A NM_006766.5 conservative_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.43
• 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: Benign. The variant received -11 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006766.5. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 8-41934352-GCTC-G is Benign according to our data. Variant chr8-41934352-GCTC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 377124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 36 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.3865_3867delGAG	p.Glu1289del	conservative_inframe_deletion	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.3865_3867delGAG	p.Glu1289del	conservative_inframe_deletion	Exon 17 of 17	ENSP00000265713.2	Q92794
	KAT6A	ENST00000406337.6	TSL:5	c.3871_3873delGAG	p.Glu1291del	conservative_inframe_deletion	Exon 18 of 18	ENSP00000385888.2	A0A3F2YNX6
	KAT6A	ENST00000396930.4	TSL:5	c.3865_3867delGAG	p.Glu1289del	conservative_inframe_deletion	Exon 18 of 18	ENSP00000380136.3	Q92794

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 151896 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000168 AC: 42 AN: 249450 AF XY: 0.000163

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000233

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000132 AC: 193 AN: 1461882 Hom.: 0 AF XY: 0.000125 AC XY: 91 AN XY: 727240

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000514 AC: 23 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000147 AC: 164 AN: 1112004

Other (OTH) AF: 0.0000828 AC: 5 AN: 60396

GnomAD4 genome AF: 0.000237 AC: 36 AN: 151896 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74170

African (AFR) AF: 0.00 AC: 0 AN: 41332

American (AMR) AF: 0.00125 AC: 19 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000260 Hom.: 0

Bravo AF: 0.000249

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4
Mutation Taster		=85/15	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: rs747034971; hg19: chr8-41791870; COSMIC: COSV55911302; COSMIC: COSV55911302;