NM_182710.3:c.129C>T

Variant names:

• chr11-65712396-C-T
• rs145735863
• NM_182710.3:c.129C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_182710.3(KAT5):​c.129C>T​(p.Gly43Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,584,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: KAT5 NM_182710.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.25
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 11-65712396-C-T is Benign according to our data. Variant chr11-65712396-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2641967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.25 with no splicing effect.
• BS2: High AC in GnomAd4 at 70 AD gene.

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.129C>T	p.Gly43Gly	synonymous	Exon 1 of 13	NP_874369.1	Q92993-3
	KAT5	NM_006388.4		c.30C>T	p.Gly10Gly	synonymous	Exon 2 of 14	NP_006379.2
	KAT5	NM_001206833.2		c.129C>T	p.Gly43Gly	synonymous	Exon 1 of 12	NP_001193762.1	Q92993-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT5	ENST00000341318.9	TSL:1 MANE Select	c.129C>T	p.Gly43Gly	synonymous	Exon 1 of 13	ENSP00000340330.4	Q92993-3
	KAT5	ENST00000377046.7	TSL:1	c.30C>T	p.Gly10Gly	synonymous	Exon 2 of 14	ENSP00000366245.3	Q92993-1
	KAT5	ENST00000530446.5	TSL:1	c.129C>T	p.Gly43Gly	synonymous	Exon 1 of 12	ENSP00000434765.1	Q92993-4

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152102 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000824

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000349 AC: 76 AN: 217928 AF XY: 0.000308

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00178

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000341

Gnomad NFE exome AF: 0.000526

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000350 AC: 502 AN: 1432718 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 259 AN XY: 713270

African (AFR) AF: 0.0000321 AC: 1 AN: 31192

American (AMR) AF: 0.00 AC: 0 AN: 34492

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 51 AN: 24680

East Asian (EAS) AF: 0.0000261 AC: 1 AN: 38370

South Asian (SAS) AF: 0.00 AC: 0 AN: 82390

European-Finnish (FIN) AF: 0.000377 AC: 20 AN: 53006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.000368 AC: 406 AN: 1103940

Other (OTH) AF: 0.000390 AC: 23 AN: 59014

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152102 Hom.: 0 Cov.: 31 AF XY: 0.000417 AC XY: 31 AN XY: 74328

African (AFR) AF: 0.0000724 AC: 3 AN: 41426

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000824 AC: 56 AN: 68002

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000782 Hom.: 0

Bravo AF: 0.000249

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		2.3
PromoterAI		-0.013	Neutral
Mutation Taster		=99/1	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: rs145735863; hg19: chr11-65479867;