10-75020544-C-T

Variant names:

• chr10-75020544-C-T
• rs11001246
• NM_012330.4:c.2630-38C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012330.4(KAT6B):​c.2630-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 1,421,902 control chromosomes in the GnomAD database, including 3,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (232 hom., cov: 32)
  • Exomes 𝑓: 0.043 (3057 hom.)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.103
• Publications: 3 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

ENSG00000234149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-75020544-C-T is Benign according to our data. Variant chr10-75020544-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6B	NM_012330.4	c.2630-38C>T		intron_variant	Intron 13 of 17	ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10	c.2630-38C>T		intron_variant	Intron 13 of 17	1	NM_012330.4	ENSP00000287239.4

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4495 AN: 152186 Hom.: 232 Cov.: 32

Gnomad AFR AF: 0.00589

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0544 AC: 13459 AN: 247462 AF XY: 0.0638

Gnomad AFR exome AF: 0.00442

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.0457

Gnomad EAS exome AF: 0.0717

Gnomad FIN exome AF: 0.0200

Gnomad NFE exome AF: 0.0279

Gnomad OTH exome AF: 0.0431

GnomAD4 exome AF: 0.0430 AC: 54656 AN: 1269598 Hom.: 3057 Cov.: 18 AF XY: 0.0492 AC XY: 31534 AN XY: 641466

African (AFR) AF: 0.00500 AC: 148 AN: 29616

American (AMR) AF: 0.0163 AC: 723 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.0437 AC: 1087 AN: 24868

East Asian (EAS) AF: 0.0696 AC: 2697 AN: 38752

South Asian (SAS) AF: 0.230 AC: 18891 AN: 82174

European-Finnish (FIN) AF: 0.0204 AC: 1078 AN: 52848

Middle Eastern (MID) AF: 0.0576 AC: 310 AN: 5382

European-Non Finnish (NFE) AF: 0.0291 AC: 27263 AN: 937568

Other (OTH) AF: 0.0456 AC: 2459 AN: 53964

GnomAD4 genome AF: 0.0295 AC: 4496 AN: 152304 Hom.: 232 Cov.: 32 AF XY: 0.0331 AC XY: 2465 AN XY: 74466

African (AFR) AF: 0.00587 AC: 244 AN: 41576

American (AMR) AF: 0.0206 AC: 315 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3468

East Asian (EAS) AF: 0.0654 AC: 339 AN: 5186

South Asian (SAS) AF: 0.246 AC: 1185 AN: 4812

European-Finnish (FIN) AF: 0.0216 AC: 229 AN: 10610

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0288 AC: 1960 AN: 68022

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0229 Hom.: 18

Bravo AF: 0.0227

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		0.10
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: rs11001246; hg19: chr10-76780302;