20-18162773-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP2 BP4_Strong BS2

The NM_001392073.1(KAT14):​c.1496C>T​(p.Ala499Val) variant causes a missense change. The variant allele was found at a frequency of 0.00244 in 1,614,114 control chromosomes in the GnomAD database, including 11 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 0.0018 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (9 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: Benign. The variant received -7 ACMG points.

• 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=0.027242273).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT14	NM_001392073.1	c.1496C>T	p.Ala499Val	missense_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.1496C>T	p.Ala499Val	missense_variant	Exon 7 of 11		NM_001392073.1	ENSP00000508684.1

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152106 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00335

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.00176 AC: 442 AN: 251282 AF XY: 0.00178

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00148

Gnomad NFE exome AF: 0.00302

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00250 AC: 3656 AN: 1461890 Hom.: 9 Cov.: 34 AF XY: 0.00243 AC XY: 1765 AN XY: 727248

African (AFR) AF: 0.000418 AC: 14 AN: 33480

American (AMR) AF: 0.000648 AC: 29 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 31 AN: 26136

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00185 AC: 99 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00303 AC: 3370 AN: 1112010

Other (OTH) AF: 0.00184 AC: 111 AN: 60396

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152224 Hom.: 2 Cov.: 33 AF XY: 0.00152 AC XY: 113 AN XY: 74414

African (AFR) AF: 0.000530 AC: 22 AN: 41542

American (AMR) AF: 0.000590 AC: 9 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00335 AC: 228 AN: 68022

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.00264 Hom.: 1

Bravo AF: 0.00168

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00186 AC: 226

EpiCase AF: 0.00256

EpiControl AF: 0.00279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.062	T;.;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.027	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;.
PhyloP100		5.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.11	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.75	T;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		0.93	P;.;P
Vest4		0.80
MVP		0.50
MPC		0.20
ClinPred		0.042	T
GERP RS		6.2
Varity_R		0.12
gMVP		0.43
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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; COSMIC: COSV99072866;