20-18162473-T-C

Variant names:

• chr20-18162473-T-C
• rs1205193
• NM_001392073.1:c.1196T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_001392073.1(KAT14):​c.1196T>C​(p.Val399Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KAT14 NM_001392073.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 30 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: Likely_benign. The variant received -1 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.
• BP4: Computational evidence support a benign effect (MetaRNN=0.066640645).

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.1196T>C	p.Val399Ala	missense	Exon 7 of 11	NP_001379002.1	A0A075B6H4
	KAT14	NM_001384192.3		c.1199T>C	p.Val400Ala	missense	Exon 7 of 11	NP_001371121.2	Q9H8E8-1
	KAT14	NM_001392069.1		c.1199T>C	p.Val400Ala	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.1196T>C	p.Val399Ala	missense	Exon 7 of 11	ENSP00000508684.1	A0A075B6H4
	KAT14	ENST00000435364.8	TSL:1	c.1199T>C	p.Val400Ala	missense	Exon 7 of 11	ENSP00000392318.2	Q9H8E8-1
	KAT14	ENST00000489634.2	TSL:1	c.815T>C	p.Val272Ala	missense	Exon 5 of 9	ENSP00000425909.2	Q9H8E8-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 102

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	20
DANN	Benign	0.72
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.1
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.027
MutPred		0.26		Loss of sheet (P = 0.0104)
MVP		0.23
MPC		0.24
ClinPred		0.27	T
GERP RS		6.0
Varity_R		0.020
gMVP		0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1205193; hg19: chr20-18143117;