rs948140872

Variant names:

• chr17-42117690-C-A
• NM_021078.3:c.1416G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-42117690-C-A
• chr17-42117690-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021078.3(KAT2A):​c.1416G>T​(p.Met472Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,298 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KAT2A NM_021078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT2A	NM_021078.3	c.1416G>T	p.Met472Ile	missense_variant	Exon 9 of 18	ENST00000225916.10	NP_066564.2
KAT2A	NM_001376227.1	c.1416G>T	p.Met472Ile	missense_variant	Exon 9 of 18		NP_001363156.1
KAT2A	XM_006721818.5	c.333G>T	p.Met111Ile	missense_variant	Exon 4 of 13		XP_006721881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT2A	ENST00000225916.10	c.1416G>T	p.Met472Ile	missense_variant	Exon 9 of 18	1	NM_021078.3	ENSP00000225916.5
KAT2A	ENST00000465682.5	n.*530G>T		non_coding_transcript_exon_variant	Exon 9 of 18	5		ENSP00000468390.1
KAT2A	ENST00000465682.5	n.*530G>T		3_prime_UTR_variant	Exon 9 of 18	5		ENSP00000468390.1
KAT2A	ENST00000592310.1	n.-201G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458298 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724914

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.26
Sift	Benign	0.057	T
Sift4G	Benign	0.13	T
Polyphen		0.048	B
Vest4		0.67
MutPred		0.30		Loss of disorder (P = 0.0568);
MVP		0.46
MPC		1.1
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.52
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40269708;