rs992030146

Variant names:

• chr11-65712316-G-C
• rs992030146
• NM_182710.3:c.49G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-65712316-G-C
• chr11-65712316-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182710.3(KAT5):​c.49G>C​(p.Gly17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,336,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G17W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: KAT5 NM_182710.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31393772).

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.49G>C	p.Gly17Arg	missense	Exon 1 of 13	NP_874369.1	Q92993-3
	KAT5	NM_001206833.2		c.49G>C	p.Gly17Arg	missense	Exon 1 of 12	NP_001193762.1	Q92993-4
	KAT5	NM_006388.4		c.12+37G>C		intron	N/A	NP_006379.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT5	ENST00000341318.9	TSL:1 MANE Select	c.49G>C	p.Gly17Arg	missense	Exon 1 of 13	ENSP00000340330.4	Q92993-3
	KAT5	ENST00000530446.5	TSL:1	c.49G>C	p.Gly17Arg	missense	Exon 1 of 12	ENSP00000434765.1	Q92993-4
	KAT5	ENST00000377046.7	TSL:1	c.12+37G>C		intron	N/A	ENSP00000366245.3	Q92993-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000225 AC: 3 AN: 1336178 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 655612

African (AFR) AF: 0.00 AC: 0 AN: 27870

American (AMR) AF: 0.00 AC: 0 AN: 16782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22034

East Asian (EAS) AF: 0.00 AC: 0 AN: 33728

South Asian (SAS) AF: 0.00 AC: 0 AN: 68524

European-Finnish (FIN) AF: 0.0000201 AC: 1 AN: 49736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4906

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1057592

Other (OTH) AF: 0.00 AC: 0 AN: 55006

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.77	T
PhyloP100		1.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.58	T
Polyphen		1.0	D
Vest4		0.26
MutPred		0.16		Gain of MoRF binding (P = 0.0065)
MVP		0.83
MPC		2.1
ClinPred		1.0	D
GERP RS		4.8
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
gMVP		0.44
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs992030146; hg19: chr11-65479787;