16-31120249-A-G

Position:

• chr16-31120249-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PP3 PP5_Moderate

The NM_032188.3(KAT8):​c.275A>G​(p.His92Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KAT8 NM_032188.3 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.37

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a domain Tudor-knot (size 55) in uniprot entity KAT8_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_032188.3
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795
• PP5: Variant 16-31120249-A-G is Pathogenic according to our data. Variant chr16-31120249-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 1684624.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT8	NM_032188.3	c.275A>G	p.His92Arg	missense_variant	2/11	ENST00000219797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT8	ENST00000219797.9	c.275A>G	p.His92Arg	missense_variant	2/11	1	NM_032188.3	P1
KAT8	ENST00000448516.6	c.275A>G	p.His92Arg	missense_variant	2/10	1
KAT8	ENST00000543774.6	c.275A>G	p.His92Arg	missense_variant	3/12	5		P1
KAT8	ENST00000539683.2	n.260A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Li-Ghorbani-Weisz-Hubshman syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Laboratory of Medical Genetics, National & Kapodistrian University of Athens

May 23, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;.;D
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Pathogenic	3.0	M;M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.85	D
Sift4G	Benign	0.063	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.69
MutPred		0.64		Gain of MoRF binding (P = 0.0233);Gain of MoRF binding (P = 0.0233);Gain of MoRF binding (P = 0.0233);
MVP		0.84
MPC		2.4
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.56		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.56		Position offset: -5

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: chr16-31131570;