17-49798330-A-G

Position:

• chr17-49798330-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_007067.5(KAT7):​c.352A>G​(p.Thr118Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: KAT7 NM_007067.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.736

Genes affected

KAT7 (HGNC:17016): (lysine acetyltransferase 7) The protein encoded by this gene is part of the multimeric HBO1 complex, which possesses histone H4-specific acetyltransferase activity. This activity is required for functional replication origins and is involved in transcriptional activation of some genes. In both cases, the acetylation of histone H4 helps unfold chromatin so that the DNA can be accessed and replicated or transcribed. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.038150102).
• BS2: High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT7	NM_007067.5	c.352A>G	p.Thr118Ala	missense_variant	4/15	ENST00000259021.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT7	ENST00000259021.9	c.352A>G	p.Thr118Ala	missense_variant	4/15	1	NM_007067.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461538 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727032

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

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

Ambry Genetics

Mar 06, 2023

The c.352A>G (p.T118A) alteration is located in exon 4 (coding exon 4) of the KAT7 gene. This alteration results from a A to G substitution at nucleotide position 352, causing the threonine (T) at amino acid position 118 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.7
DANN	Benign	0.71
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	D;D;D;D;D;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.45	N;N
REVEL	Benign	0.029
Sift	Benign	0.67	T;T
Sift4G	Benign	0.79	T;T
Polyphen		0.0	B;.
Vest4		0.053
MutPred		0.19		Loss of phosphorylation at T118 (P = 0.0038);Loss of phosphorylation at T118 (P = 0.0038);
MVP		0.082
MPC		0.76
ClinPred		0.042	T
GERP RS		2.7
Varity_R		0.025
gMVP		0.10

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: chr17-47875692;