rs569172957

Variant names:

• chr10-75022078-GGAGGAGGAGGAC-G
• rs569172957
• NM_012330.4:c.3231_3242delCGAGGAGGAGGA

Your query was ambiguous. Multiple possible variants found:

• chr10-75022078-GGAGGAGGAGGAC-G
• chr10-75022078-GGAGGAGGAGGAC-GGAGGAGGAGGACGAGGAGGAGGAC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP3 BP3 BP6 BS2

The NM_012330.4(KAT6B):​c.3231_3242delCGAGGAGGAGGA​(p.Asp1077_Glu1080del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,611,110 control chromosomes in the GnomAD database, including 8 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (8 hom.)
• Consequence: KAT6B NM_012330.4 disruptive_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:6
• Conservation: PhyloP100: 7.89
• Publications: 1 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

ENSG00000234149 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP3: Nonframeshift variant in repetitive region in NM_012330.4
• BP6: Variant 10-75022078-GGAGGAGGAGGAC-G is Benign according to our data. Variant chr10-75022078-GGAGGAGGAGGAC-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 260236.
• BS2: High AC in GnomAd4 at 363 AD gene.

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.3231_3242delCGAGGAGGAGGA	p.Asp1077_Glu1080del	disruptive_inframe_deletion	Exon 16 of 18	NP_036462.2	Q8WYB5-1
	KAT6B	NM_001370136.1		c.3231_3242delCGAGGAGGAGGA	p.Asp1077_Glu1080del	disruptive_inframe_deletion	Exon 16 of 18	NP_001357065.1	Q8WYB5-1
	KAT6B	NM_001370137.1		c.3231_3242delCGAGGAGGAGGA	p.Asp1077_Glu1080del	disruptive_inframe_deletion	Exon 16 of 18	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.3231_3242delCGAGGAGGAGGA	p.Asp1077_Glu1080del	disruptive_inframe_deletion	Exon 16 of 18	ENSP00000287239.4	Q8WYB5-1
	KAT6B	ENST00000372711.2	TSL:1	c.2682_2693delCGAGGAGGAGGA	p.Asp894_Glu897del	disruptive_inframe_deletion	Exon 16 of 18	ENSP00000361796.1	Q8WYB5-2
	KAT6B	ENST00000648725.1		c.3231_3242delCGAGGAGGAGGA	p.Asp1077_Glu1080del	disruptive_inframe_deletion	Exon 16 of 18	ENSP00000497841.1	Q8WYB5-1

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 363 AN: 151898 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00839

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00335

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00252 AC: 624 AN: 247992 AF XY: 0.00249

Gnomad AFR exome AF: 0.000570

Gnomad AMR exome AF: 0.000756

Gnomad ASJ exome AF: 0.000801

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00825

Gnomad NFE exome AF: 0.00353

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00281 AC: 4094 AN: 1459094 Hom.: 8 AF XY: 0.00270 AC XY: 1962 AN XY: 725934

African (AFR) AF: 0.000269 AC: 9 AN: 33404

American (AMR) AF: 0.000784 AC: 35 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.000804 AC: 21 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86134

European-Finnish (FIN) AF: 0.00741 AC: 395 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00316 AC: 3504 AN: 1109780

Other (OTH) AF: 0.00211 AC: 127 AN: 60278

GnomAD4 genome AF: 0.00239 AC: 363 AN: 152016 Hom.: 0 Cov.: 32 AF XY: 0.00272 AC XY: 202 AN XY: 74328

African (AFR) AF: 0.000507 AC: 21 AN: 41414

American (AMR) AF: 0.00105 AC: 16 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4802

European-Finnish (FIN) AF: 0.00839 AC: 89 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00335 AC: 228 AN: 67980

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00222 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Genitopatellar syndrome (1)
-	1	-	Genitopatellar syndrome;C1863557:Blepharophimosis - intellectual disability syndrome, SBBYS type (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.9
Mutation Taster		=184/16	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs569172957; hg19: chr10-76781836;