NM_012330.4:c.-258-101delT

Variant names:

• chr10-74842497-CT-C
• rs55787052
• NM_012330.4:c.-258-101delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012330.4(KAT6B):​c.-258-101delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 519,738 control chromosomes in the GnomAD database, including 21,386 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (12529 hom., cov: 25)
  • Exomes 𝑓: 0.17 (8857 hom.)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.663
• Publications: 0 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
• multiple congenital anomalies/dysmorphic 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 -10 ACMG points.

• BP6: Variant 10-74842497-CT-C is Benign according to our data. Variant chr10-74842497-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1237197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012330.4. 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
	KAT6B	NM_012330.4	MANE Select	c.-258-101delT		intron	N/A	NP_036462.2	Q8WYB5-1
	KAT6B	NM_001370136.1		c.-258-101delT		intron	N/A	NP_001357065.1	Q8WYB5-1
	KAT6B	NM_001370137.1		c.-258-101delT		intron	N/A	NP_001357066.1	Q8WYB5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT6B	ENST00000287239.10	TSL:1 MANE Select	c.-258-102delT		intron	N/A	ENSP00000287239.4	Q8WYB5-1
	KAT6B	ENST00000372711.2	TSL:1	c.-258-102delT		intron	N/A	ENSP00000361796.1	Q8WYB5-2
	KAT6B	ENST00000648725.1		c.-258-102delT		intron	N/A	ENSP00000497841.1	Q8WYB5-1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46378 AN: 151944 Hom.: 12485 Cov.: 25

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.170 AC: 62549 AN: 367676 Hom.: 8857 AF XY: 0.175 AC XY: 33359 AN XY: 190120

African (AFR) AF: 0.704 AC: 7294 AN: 10360

American (AMR) AF: 0.289 AC: 3436 AN: 11888

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 1652 AN: 12044

East Asian (EAS) AF: 0.336 AC: 9381 AN: 27932

South Asian (SAS) AF: 0.387 AC: 9657 AN: 24946

European-Finnish (FIN) AF: 0.0536 AC: 1435 AN: 26748

Middle Eastern (MID) AF: 0.231 AC: 398 AN: 1724

European-Non Finnish (NFE) AF: 0.109 AC: 25043 AN: 229634

Other (OTH) AF: 0.190 AC: 4253 AN: 22400

GnomAD4 genome AF: 0.306 AC: 46474 AN: 152062 Hom.: 12529 Cov.: 25 AF XY: 0.303 AC XY: 22528 AN XY: 74368

African (AFR) AF: 0.712 AC: 29499 AN: 41418

American (AMR) AF: 0.278 AC: 4241 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1579 AN: 5174

South Asian (SAS) AF: 0.422 AC: 2031 AN: 4816

European-Finnish (FIN) AF: 0.0513 AC: 544 AN: 10594

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7429 AN: 67992

Other (OTH) AF: 0.267 AC: 565 AN: 2114

Alfa AF: 0.212 Hom.: 887

Bravo AF: 0.334

Asia WGS AF: 0.386 AC: 1338 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66
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: rs55787052; hg19: chr10-76602255;