rs17659391

Variant names:

• chr17-42114921-G-A
• rs17659391
• NM_021078.3:c.1990C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-42114921-G-A
• chr17-42114921-G-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_021078.3(KAT2A):​c.1990C>T​(p.Leu664Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0652 in 1,613,768 control chromosomes in the GnomAD database, including 4,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (291 hom., cov: 32)
  • Exomes 𝑓: 0.067 (3892 hom.)
• Consequence: KAT2A NM_021078.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.35
• Publications: 11 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 17-42114921-G-A is Benign according to our data. Variant chr17-42114921-G-A is described in ClinVar as Benign. ClinVar VariationId is 1249415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

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.1990C>T	p.Leu664Leu	synonymous	Exon 13 of 18	NP_066564.2	Q92830-1
	KAT2A	NM_001376227.1		c.1990C>T	p.Leu664Leu	synonymous	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.1990C>T	p.Leu664Leu	synonymous	Exon 13 of 18	ENSP00000225916.5	Q92830-1
	KAT2A	ENST00000873177.1		c.1990C>T	p.Leu664Leu	synonymous	Exon 13 of 18	ENSP00000543236.1
	KAT2A	ENST00000873169.1		c.2002C>T	p.Leu668Leu	synonymous	Exon 13 of 18	ENSP00000543228.1

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7626 AN: 152126 Hom.: 291 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0283

GnomAD2 exomes AF: 0.0517 AC: 13004 AN: 251290 AF XY: 0.0506

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.0193

Gnomad ASJ exome AF: 0.0236

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.0754

Gnomad OTH exome AF: 0.0569

GnomAD4 exome AF: 0.0668 AC: 97665 AN: 1461524 Hom.: 3892 Cov.: 32 AF XY: 0.0649 AC XY: 47201 AN XY: 727084

African (AFR) AF: 0.00986 AC: 330 AN: 33478

American (AMR) AF: 0.0197 AC: 881 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0261 AC: 681 AN: 26124

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39692

South Asian (SAS) AF: 0.0117 AC: 1011 AN: 86258

European-Finnish (FIN) AF: 0.121 AC: 6453 AN: 53410

Middle Eastern (MID) AF: 0.0127 AC: 73 AN: 5768

European-Non Finnish (NFE) AF: 0.0761 AC: 84618 AN: 1111700

Other (OTH) AF: 0.0598 AC: 3613 AN: 60386

GnomAD4 genome AF: 0.0501 AC: 7622 AN: 152244 Hom.: 291 Cov.: 32 AF XY: 0.0489 AC XY: 3642 AN XY: 74434

African (AFR) AF: 0.0128 AC: 530 AN: 41536

American (AMR) AF: 0.0265 AC: 405 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4824

European-Finnish (FIN) AF: 0.117 AC: 1236 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0762 AC: 5183 AN: 68012

Other (OTH) AF: 0.0270 AC: 57 AN: 2108

Alfa AF: 0.0613 Hom.: 656

Bravo AF: 0.0423

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0662

EpiControl AF: 0.0625

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs17659391; hg19: chr17-40266939;