10-74842961-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP6_Moderate BS1 BS2

The NM_012330.4(KAT6B):c.104C>T(p.Ala35Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: KAT6B NM_012330.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, KAT6B
• BP6: Variant 10-74842961-C-T is Benign according to our data. Variant chr10-74842961-C-T is described in ClinVar as [Benign]. Clinvar id is 2051769.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000301 (44/1461868) while in subpopulation MID AF= 0.000173 (1/5768). AF 95% confidence interval is 0.0000245. There are 0 homozygotes in gnomad4_exome. There are 18 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAdExome at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT6B	NM_012330.4	c.104C>T	p.Ala35Val	missense_variant	3/18	ENST00000287239.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT6B	ENST00000287239.10	c.104C>T	p.Ala35Val	missense_variant	3/18	1	NM_012330.4	P2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251454 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135902

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000508 Hom.: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Genitopatellar syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 03, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Pathogenic	0.25
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.24	D
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
Polyphen		1.0	.;D;.;D;D;D;.;.;.;.;.;D;.;D;.;D;D;.;.;.;.;.;.;D;.
Vest4		0.84, 0.82, 0.74, 0.85, 0.91
MutPred		0.25		Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);
MVP		0.85
MPC		1.0
ClinPred		0.84	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.74

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: rs772997103; hg19: chr10-76602719; COSMIC: COSV54751269; COSMIC: COSV54751269;