Genetic Variant KAT14:p.Pro740Pro (chr20-18187333-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_001392073.1(KAT14):c.2220C>T(p.Pro740Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,613,928 control chromosomes in the GnomAD database, including 269 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 0.014 ( 22 hom., cov: 33)

Exomes 𝑓: 0.017 ( 247 hom. )

Consequence

KAT14
NM_001392073.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.97

Publications

14 publications found

Variant links:

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

KAT14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP7

Synonymous conserved (PhyloP=-4.97 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.014 (2136/152332) while in subpopulation AMR AF = 0.0214 (328/15308). AF 95% confidence interval is 0.0195. There are 22 homozygotes in GnomAd4. There are 1081 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT14	NM_001392073.1 link	c.2220C>T	p.Pro740Pro	synonymous_variant	Exon 11 of 11	ENST00000688188.1	NP_001379002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT14	ENST00000688188.1 link	c.2220C>T	p.Pro740Pro	synonymous_variant	Exon 11 of 11		NM_001392073.1	ENSP00000508684.1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2136

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00425

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0144

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0192

Gnomad OTH

AF:

0.0172

GnomAD4 exome

AF:

0.0167

AC:

24390

AN:

1461596

Hom.:

247

Cov.:

AF XY:

0.0165

AC XY:

12022

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.00368

AC:

123

AN:

33468

American (AMR)

AF:

0.0119

AC:

533

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.0276

AC:

721

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.00429

AC:

370

AN:

86164

European-Finnish (FIN)

AF:

0.0154

AC:

820

AN:

53416

Middle Eastern (MID)

AF:

0.0283

AC:

163

AN:

5768

European-Non Finnish (NFE)

AF:

0.0186

AC:

20713

AN:

1111906

Other (OTH)

AF:

0.0157

AC:

946

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1655

3310

4966

6621

8276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0140

AC:

2136

AN:

152332

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1081

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00423

AC:

176

AN:

41574

American (AMR)

AF:

0.0214

AC:

328

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00518

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0144

AC:

153

AN:

10612

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0192

AC:

1303

AN:

68026

Other (OTH)

AF:

0.0170

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

117

234

352

469

586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.8

(source)

PhyloP100

-5.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over