rs10490992

Variant names:

• chr10-74972275-C-T
• rs10490992
• NM_012330.4:c.929-232C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012330.4(KAT6B):​c.929-232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 152,058 control chromosomes in the GnomAD database, including 593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.061 (593 hom., cov: 32)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.469
• Publications: 2 publications found

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]

KAT6B Gene-Disease associations (from GenCC):

• blepharophimosis - intellectual disability syndrome, SBBYS type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• genitopatellar syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• KAT6B-related multiple congenital anomalies syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• RASopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-74972275-C-T is Benign according to our data. Variant chr10-74972275-C-T is described in ClinVar as Benign. ClinVar VariationId is 561615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6B	NM_012330.4	c.929-232C>T		intron_variant	Intron 6 of 17	ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10	c.929-232C>T		intron_variant	Intron 6 of 17	1	NM_012330.4	ENSP00000287239.4

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9174 AN: 151938 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0113

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00819

Gnomad OTH AF: 0.0513

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

GnomAD4 genome AF: 0.0605 AC: 9207 AN: 152058 Hom.: 593 Cov.: 32 AF XY: 0.0623 AC XY: 4628 AN XY: 74336

African (AFR) AF: 0.138 AC: 5702 AN: 41442

American (AMR) AF: 0.0834 AC: 1274 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3468

East Asian (EAS) AF: 0.159 AC: 823 AN: 5164

South Asian (SAS) AF: 0.103 AC: 495 AN: 4818

European-Finnish (FIN) AF: 0.0113 AC: 120 AN: 10580

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00819 AC: 557 AN: 68004

Other (OTH) AF: 0.0531 AC: 112 AN: 2108

Alfa AF: 0.0348 Hom.: 118

Bravo AF: 0.0688

Asia WGS AF: 0.135 AC: 469 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
DANN	Benign	0.64
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs10490992; hg19: chr10-76732033;