16-31120219-A-G

Position:

• chr16-31120219-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032188.3(KAT8):​c.245A>G​(p.Asp82Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KAT8 NM_032188.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.54

Genes affected

KAT8 (HGNC:17933): (lysine acetyltransferase 8) This gene encodes a member of the MYST histone acetylase protein family. The encoded protein has a characteristic MYST domain containing an acetyl-CoA-binding site, a chromodomain typical of proteins which bind histones, and a C2HC-type zinc finger. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17340225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT8	NM_032188.3	c.245A>G	p.Asp82Gly	missense_variant	2/11	ENST00000219797.9	NP_115564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT8	ENST00000219797.9	c.245A>G	p.Asp82Gly	missense_variant	2/11	1	NM_032188.3	ENSP00000219797.3
KAT8	ENST00000448516.6	c.245A>G	p.Asp82Gly	missense_variant	2/10	1		ENSP00000406037.2
KAT8	ENST00000543774.6	c.245A>G	p.Asp82Gly	missense_variant	3/12	5		ENSP00000456933.2
KAT8	ENST00000539683.2	n.230A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 17, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.;T
Eigen	Benign	0.085
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L;L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.5	.;D;D
REVEL	Benign	0.14
Sift	Benign	0.20	.;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.049	B;.;B
Vest4		0.19
MutPred		0.29		Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);
MVP		0.20
MPC		1.3
ClinPred		0.89	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-31131540;