20-18162711-C-T

Variant names:

• chr20-18162711-C-T
• rs1205194
• NM_001392073.1:c.1434C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001392073.1(KAT14):​c.1434C>T​(p.Pro478Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,614,012 control chromosomes in the GnomAD database, including 63,983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4817 hom., cov: 33)
  • Exomes 𝑓: 0.27 (59166 hom.)
• Consequence: KAT14 NM_001392073.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 18 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.077 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT14	NM_001392073.1	c.1434C>T	p.Pro478Pro	synonymous_variant	Exon 7 of 11	ENST00000688188.1	NP_001379002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT14	ENST00000688188.1	c.1434C>T	p.Pro478Pro	synonymous_variant	Exon 7 of 11		NM_001392073.1	ENSP00000508684.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35101 AN: 152030 Hom.: 4815 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.206

GnomAD2 exomes AF: 0.291 AC: 72985 AN: 251180 AF XY: 0.293

Gnomad AFR exome AF: 0.0937

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.487

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.275 AC: 401738 AN: 1461864 Hom.: 59166 Cov.: 43 AF XY: 0.278 AC XY: 202486 AN XY: 727224

African (AFR) AF: 0.0929 AC: 3110 AN: 33478

American (AMR) AF: 0.308 AC: 13771 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4317 AN: 26136

East Asian (EAS) AF: 0.552 AC: 21898 AN: 39698

South Asian (SAS) AF: 0.385 AC: 33196 AN: 86250

European-Finnish (FIN) AF: 0.333 AC: 17793 AN: 53420

Middle Eastern (MID) AF: 0.196 AC: 1128 AN: 5768

European-Non Finnish (NFE) AF: 0.261 AC: 290192 AN: 1112000

Other (OTH) AF: 0.270 AC: 16333 AN: 60394

GnomAD4 genome AF: 0.231 AC: 35103 AN: 152148 Hom.: 4817 Cov.: 33 AF XY: 0.238 AC XY: 17716 AN XY: 74376

African (AFR) AF: 0.100 AC: 4166 AN: 41518

American (AMR) AF: 0.266 AC: 4069 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3468

East Asian (EAS) AF: 0.508 AC: 2626 AN: 5172

South Asian (SAS) AF: 0.394 AC: 1903 AN: 4824

European-Finnish (FIN) AF: 0.328 AC: 3467 AN: 10572

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17629 AN: 67992

Other (OTH) AF: 0.205 AC: 434 AN: 2112

Alfa AF: 0.245 Hom.: 11249

Bravo AF: 0.220

Asia WGS AF: 0.405 AC: 1405 AN: 3478

EpiCase AF: 0.245

EpiControl AF: 0.236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.4
DANN	Benign	0.73
PhyloP100		-0.077
Mutation Taster		=100/0	polymorphism (auto)

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: rs1205194; hg19: chr20-18143355; COSMIC: COSV108227140;