rs10490994

Positions:

• chr10-75024780-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_012330.4(KAT6B):​c.3373-178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 152,230 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.033 (143 hom., cov: 32)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.13

Genes affected

KAT6B (HGNC:17582): (lysine acetyltransferase 6B) The protein encoded by this gene is a histone acetyltransferase and component of the MOZ/MORF protein complex. In addition to its acetyltransferase activity, the encoded protein has transcriptional activation activity in its N-terminal end and transcriptional repression activity in its C-terminal end. This protein is necessary for RUNX2-dependent transcriptional activation and could be involved in brain development. Mutations have been found in patients with genitopatellar syndrome. A translocation of this gene and the CREBBP gene results in acute myeloid leukemias. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 10-75024780-T-C is Benign according to our data. Variant chr10-75024780-T-C is described in ClinVar as [Benign]. Clinvar id is 1258640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6B	NM_012330.4	c.3373-178T>C		intron_variant		ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10	c.3373-178T>C		intron_variant		1	NM_012330.4	ENSP00000287239	P2
	ENST00000413431.1	n.65+330A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4960 AN: 152112 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.0579

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0326 AC: 4962 AN: 152230 Hom.: 143 Cov.: 32 AF XY: 0.0339 AC XY: 2521 AN XY: 74432

Gnomad4 AFR AF: 0.0579

Gnomad4 AMR AF: 0.0446

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.0825

Gnomad4 SAS AF: 0.0288

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0177 Hom.: 64

Bravo AF: 0.0368

Asia WGS AF: 0.0580 AC: 200 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.76

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: rs10490994; hg19: chr10-76784538;