rs4645914

Variant names:

• chr11-65712785-C-T
• rs4645914
• NM_182710.3:c.198C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_182710.3(KAT5):​c.198C>T​(p.Ser66Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,613,992 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (90 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (92 hom.)
• Consequence: KAT5 NM_182710.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.196
• Publications: 1 publications found

Genes affected

KAT5 (HGNC:5275): (lysine acetyltransferase 5) The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was originally isolated as an HIV-1 TAT-interactive protein. HATs play important roles in regulating chromatin remodeling, transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

KAT5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.147).
• BP6: Variant 11-65712785-C-T is Benign according to our data. Variant chr11-65712785-C-T is described in ClinVar as Benign. ClinVar VariationId is 776626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.196 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182710.3. 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
	KAT5	NM_182710.3	MANE Select	c.198C>T	p.Ser66Ser	synonymous	Exon 2 of 13	NP_874369.1	Q92993-3
	KAT5	NM_006388.4		c.99C>T	p.Ser33Ser	synonymous	Exon 3 of 14	NP_006379.2
	KAT5	NM_001206833.2		c.198C>T	p.Ser66Ser	synonymous	Exon 2 of 12	NP_001193762.1	Q92993-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT5	ENST00000341318.9	TSL:1 MANE Select	c.198C>T	p.Ser66Ser	synonymous	Exon 2 of 13	ENSP00000340330.4	Q92993-3
	KAT5	ENST00000377046.7	TSL:1	c.99C>T	p.Ser33Ser	synonymous	Exon 3 of 14	ENSP00000366245.3	Q92993-1
	KAT5	ENST00000530446.5	TSL:1	c.198C>T	p.Ser66Ser	synonymous	Exon 2 of 12	ENSP00000434765.1	Q92993-4

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2663 AN: 152014 Hom.: 90 Cov.: 31

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00910

GnomAD2 exomes AF: 0.00449 AC: 1130 AN: 251474 AF XY: 0.00333

Gnomad AFR exome AF: 0.0636

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00173 AC: 2528 AN: 1461860 Hom.: 92 Cov.: 33 AF XY: 0.00153 AC XY: 1113 AN XY: 727232

African (AFR) AF: 0.0645 AC: 2158 AN: 33474

American (AMR) AF: 0.00212 AC: 95 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5756

European-Non Finnish (NFE) AF: 0.0000638 AC: 71 AN: 1112006

Other (OTH) AF: 0.00316 AC: 191 AN: 60392

GnomAD4 genome AF: 0.0175 AC: 2663 AN: 152132 Hom.: 90 Cov.: 31 AF XY: 0.0168 AC XY: 1253 AN XY: 74400

African (AFR) AF: 0.0618 AC: 2565 AN: 41492

American (AMR) AF: 0.00471 AC: 72 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67984

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00796 Hom.: 20

Bravo AF: 0.0204

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

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	-0.44
CADD	Benign	9.6
DANN	Benign	0.90
PhyloP100		0.20
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4645914; hg19: chr11-65480256;