chr20-18162473-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP2 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. 14/21 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
• 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: Benign. The variant received -11 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=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 rank	MANE	Protein	UniProt
KAT14	NM_001392073.1	c.1196T>G	p.Val399Gly	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.1196T>G	p.Val399Gly	missense_variant	Exon 7 of 11		NM_001392073.1	ENSP00000508684.1

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

GnomAD2 exomes AF: 0.984 AC: 247112 AN: 251234 AF XY: 0.983

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 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

African (AFR) AF: 0.996 AC: 33335 AN: 33480

American (AMR) AF: 0.987 AC: 44151 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 25426 AN: 26134

East Asian (EAS) AF: 1.00 AC: 39695 AN: 39696

South Asian (SAS) AF: 0.993 AC: 85675 AN: 86256

European-Finnish (FIN) AF: 0.985 AC: 52600 AN: 53416

Middle Eastern (MID) AF: 0.963 AC: 5554 AN: 5768

European-Non Finnish (NFE) AF: 0.977 AC: 1085901 AN: 1111998

Other (OTH) AF: 0.982 AC: 59292 AN: 60394

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

African (AFR) AF: 0.995 AC: 41320 AN: 41522

American (AMR) AF: 0.977 AC: 14942 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 3380 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5170

South Asian (SAS) AF: 0.992 AC: 4782 AN: 4820

European-Finnish (FIN) AF: 0.986 AC: 10460 AN: 10604

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.977 AC: 66473 AN: 68034

Other (OTH) AF: 0.982 AC: 2075 AN: 2112

Alfa AF: 0.979 Hom.: 151145

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;.;.
PhyloP100		4.1
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1205193; hg19: chr20-18143117; COSMIC: COSV108227139;