chr20-18162473-T-G

Position:

• chr20-18162473-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001392073.1(KAT14):​c.1196T>G​(p.Val399Gly) variant causes a missense change. The variant allele was found at a frequency of 0.98 in 1,614,088 control chromosomes in the GnomAD database, including 774,757 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.98 (73697 hom., cov: 31)
  • Exomes 𝑓: 0.98 (701060 hom.)
• Consequence: KAT14 NM_001392073.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.7861917E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT14	NM_001392073.1	c.1196T>G	p.Val399Gly	missense_variant	7/11	ENST00000688188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT14	ENST00000688188.1	c.1196T>G	p.Val399Gly	missense_variant	7/11		NM_001392073.1	A1

Frequencies

GnomAD3 genomes AF: 0.984 AC: 149667 AN: 152112 Hom.: 73637 Cov.: 31

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.977

Gnomad OTH AF: 0.982

GnomAD3 exomes AF: 0.984 AC: 247112 AN: 251234 Hom.: 121551 AF XY: 0.983 AC XY: 133504 AN XY: 135808

Gnomad AFR exome AF: 0.996

Gnomad AMR exome AF: 0.988

Gnomad ASJ exome AF: 0.974

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.994

Gnomad FIN exome AF: 0.986

Gnomad NFE exome AF: 0.976

Gnomad OTH exome AF: 0.981

GnomAD4 exome AF: 0.979 AC: 1431629 AN: 1461858 Hom.: 701060 Cov.: 102 AF XY: 0.980 AC XY: 712392 AN XY: 727234

Gnomad4 AFR exome AF: 0.996

Gnomad4 AMR exome AF: 0.987

Gnomad4 ASJ exome AF: 0.973

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.993

Gnomad4 FIN exome AF: 0.985

Gnomad4 NFE exome AF: 0.977

Gnomad4 OTH exome AF: 0.982

GnomAD4 genome AF: 0.984 AC: 149786 AN: 152230 Hom.: 73697 Cov.: 31 AF XY: 0.984 AC XY: 73210 AN XY: 74418

Gnomad4 AFR AF: 0.995

Gnomad4 AMR AF: 0.977

Gnomad4 ASJ AF: 0.974

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.992

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.977

Gnomad4 OTH AF: 0.982

Alfa AF: 0.978 Hom.: 107101

Bravo AF: 0.984

TwinsUK AF: 0.970 AC: 3598

ALSPAC AF: 0.977 AC: 3767

ESP6500AA AF: 0.994 AC: 4381

ESP6500EA AF: 0.974 AC: 8373

ExAC AF: 0.984 AC: 119407

Asia WGS AF: 0.997 AC: 3464 AN: 3476

EpiCase AF: 0.975

EpiControl AF: 0.973

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	21
DANN	Benign	0.84
DEOGEN2	Benign	0.027	T;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.026	T;T;T
MetaRNN	Benign	5.8e-7	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.69	N;.;.
MutationTaster	Benign	0.80	P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.14	N;N;N
REVEL	Benign	0.097
Sift	Benign	0.55	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.051
MPC		0.25
ClinPred		0.0049	T
GERP RS		6.0
Varity_R		0.042
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1205193; hg19: chr20-18143117;