16-31117791-C-G

Position:

• chr16-31117791-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_032188.3(KAT8):​c.110C>G​(p.Ser37Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: KAT8 NM_032188.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06

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 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity KAT8_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18178856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT8	NM_032188.3	c.110C>G	p.Ser37Cys	missense_variant	1/11	ENST00000219797.9	NP_115564.2
KAT8	NM_182958.4	c.110C>G	p.Ser37Cys	missense_variant	1/10		NP_892003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT8	ENST00000219797.9	c.110C>G	p.Ser37Cys	missense_variant	1/11	1	NM_032188.3	ENSP00000219797.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jan 17, 2024

Variant summary: MYST1 c.110C>G (p.Ser37Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 88242 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.110C>G in individuals affected with Li-Ghorbani Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.75	.;T;T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Benign	0.036
Sift	Uncertain	0.022	.;D;D
Sift4G	Uncertain	0.049	D;D;D
Polyphen		0.22	B;.;B
Vest4		0.17
MutPred		0.24		Loss of glycosylation at S37 (P = 0.0032);Loss of glycosylation at S37 (P = 0.0032);Loss of glycosylation at S37 (P = 0.0032);
MVP		0.21
MPC		1.5
ClinPred		0.64	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.21
gMVP		0.28

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: chr16-31129112;