chr17-42115004-C-A

Variant names:

• chr17-42115004-C-A
• rs781785575
• NM_021078.3:c.1907G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021078.3(KAT2A):​c.1907G>T​(p.Ser636Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S636N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KAT2A NM_021078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 0 publications found

Genes affected

KAT2A (HGNC:4201): (lysine acetyltransferase 2A) KAT2A, or GCN5, is a histone acetyltransferase (HAT) that functions primarily as a transcriptional activator. It also functions as a repressor of NF-kappa-B (see MIM 164011) by promoting ubiquitination of the NF-kappa-B subunit RELA (MIM 164014) in a HAT-independent manner (Mao et al., 2009 [PubMed 19339690]).[supplied by OMIM, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021078.3. 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
	KAT2A	NM_021078.3	MANE Select	c.1907G>T	p.Ser636Ile	missense	Exon 13 of 18	NP_066564.2	Q92830-1
	KAT2A	NM_001376227.1		c.1907G>T	p.Ser636Ile	missense	Exon 13 of 18	NP_001363156.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT2A	ENST00000225916.10	TSL:1 MANE Select	c.1907G>T	p.Ser636Ile	missense	Exon 13 of 18	ENSP00000225916.5	Q92830-1
	KAT2A	ENST00000873177.1		c.1907G>T	p.Ser636Ile	missense	Exon 13 of 18	ENSP00000543236.1
	KAT2A	ENST00000873169.1		c.1919G>T	p.Ser640Ile	missense	Exon 13 of 18	ENSP00000543228.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	D
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.19
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.022	D
Polyphen		0.93	P
Vest4		0.48
MutPred		0.36		Loss of disorder (P = 0.0148)
MVP		0.56
MPC		1.1
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs781785575; hg19: chr17-40267022; COSMIC: COSV104556709; COSMIC: COSV104556709;