chr8-41932020-G-C

Position:

• chr8-41932020-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006766.5(KAT6A):​c.*185C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 542,170 control chromosomes in the GnomAD database, including 12,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2777 hom., cov: 31)
  • Exomes 𝑓: 0.21 (10185 hom.)
• Consequence: KAT6A NM_006766.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.17

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 8-41932020-G-C is Benign according to our data. Variant chr8-41932020-G-C is described in ClinVar as [Benign]. Clinvar id is 1247574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6A	NM_006766.5	c.*185C>G		3_prime_UTR_variant	17/17	ENST00000265713.8	NP_006757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6A	ENST00000265713	c.*185C>G		3_prime_UTR_variant	17/17	1	NM_006766.5	ENSP00000265713.2
KAT6A	ENST00000406337	c.*185C>G		3_prime_UTR_variant	18/18	5		ENSP00000385888.2
KAT6A	ENST00000396930	c.*185C>G		3_prime_UTR_variant	18/18	5		ENSP00000380136.3
KAT6A	ENST00000649817	c.*185C>G		3_prime_UTR_variant	11/11			ENSP00000497780.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24955 AN: 151432 Hom.: 2777 Cov.: 31

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.215 AC: 83889 AN: 390620 Hom.: 10185 Cov.: 6 AF XY: 0.214 AC XY: 41752 AN XY: 195376

Gnomad4 AFR exome AF: 0.0508

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.000339

Gnomad4 SAS exome AF: 0.0534

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.165 AC: 24947 AN: 151550 Hom.: 2777 Cov.: 31 AF XY: 0.163 AC XY: 12041 AN XY: 74020

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0480

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.170

Alfa AF: 0.191 Hom.: 377

Bravo AF: 0.149

Asia WGS AF: 0.0290 AC: 102 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs1050991; hg19: chr8-41789538;