20-18162773-C-A

Variant names:

• chr20-18162773-C-A
• rs41276418
• NM_001392073.1:c.1496C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001392073.1(KAT14):​c.1496C>A​(p.Ala499Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A499V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KAT14 NM_001392073.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64
• Publications: 6 publications found

Genes affected

KAT14 (HGNC:15904): (lysine acetyltransferase 14) CSRP2 is a protein containing two LIM domains, which are double zinc finger motifs found in proteins of diverse function. CSRP2 and some related proteins are thought to act as protein adapters, bridging two or more proteins to form a larger protein complex. The protein encoded by this gene binds to one of the LIM domains of CSRP2 and contains an acetyltransferase domain. Although the encoded protein has been detected in the cytoplasm, it is predominantly a nuclear protein. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2011]

KAT14 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.77498 (below the threshold of 3.09). Trascript score misZ: 1.7338 (below the threshold of 3.09). GenCC associations: The gene is linked to multiple congenital anomalies/dysmorphic syndrome.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001392073.1. 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
	KAT14	NM_001392073.1	MANE Select	c.1496C>A	p.Ala499Glu	missense	Exon 7 of 11	NP_001379002.1	A0A075B6H4
	KAT14	NM_001384192.3		c.1499C>A	p.Ala500Glu	missense	Exon 7 of 11	NP_001371121.2	Q9H8E8-1
	KAT14	NM_001392069.1		c.1499C>A	p.Ala500Glu	missense	Exon 7 of 11	NP_001378998.1	Q9H8E8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT14	ENST00000688188.1	MANE Select	c.1496C>A	p.Ala499Glu	missense	Exon 7 of 11	ENSP00000508684.1	A0A075B6H4
	KAT14	ENST00000435364.8	TSL:1	c.1499C>A	p.Ala500Glu	missense	Exon 7 of 11	ENSP00000392318.2	Q9H8E8-1
	KAT14	ENST00000489634.2	TSL:1	c.1115C>A	p.Ala372Glu	missense	Exon 5 of 9	ENSP00000425909.2	Q9H8E8-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251282 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.26
Sift	Benign	0.75	T
Sift4G	Benign	1.0	T
Polyphen		0.38	B
Vest4		0.85
MutPred		0.46		Loss of helix (P = 0.0068)
MVP		0.56
MPC		0.25
ClinPred		0.38	T
GERP RS		6.2
Varity_R		0.16
gMVP		0.71
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41276418; hg19: chr20-18143417;