Variant chr2-200490383-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_152387.4(KCTD18):c.998C>T(p.Ala333Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,614,088 control chromosomes in the GnomAD database, including 37,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2681 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34591 hom. )

Consequence

KCTD18
NM_152387.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

KCTD18 (HGNC:26446): (potassium channel tetramerization domain containing 18) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

KCTD18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048826933).

BP6

Variant 2-200490383-G-A is Benign according to our data. Variant chr2-200490383-G-A is described in ClinVar as [Benign]. Clinvar id is 3058937.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD18	NM_152387.4 linkuse as main transcript	c.998C>T	p.Ala333Val	missense_variant	7/7	ENST00000359878.8	NP_689600.2	Q6PI47-1
KCTD18	NM_001321547.2 linkuse as main transcript	c.998C>T	p.Ala333Val	missense_variant	7/7		NP_001308476.1	Q6PI47-1A8K4A2
KCTD18	NM_001321548.2 linkuse as main transcript	c.371C>T	p.Ala124Val	missense_variant	7/7		NP_001308477.1
KCTD18	NM_001321550.2 linkuse as main transcript	c.371C>T	p.Ala124Val	missense_variant	7/7		NP_001308479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD18	ENST00000359878.8 linkuse as main transcript	c.998C>T	p.Ala333Val	missense_variant	7/7	1	NM_152387.4	ENSP00000352941.3		Q6PI47-1
KCTD18	ENST00000409157.5 linkuse as main transcript	c.998C>T	p.Ala333Val	missense_variant	7/7	1		ENSP00000386751.1		Q6PI47-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25275

AN:

152142

Hom.:

2684

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0664

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.175

AC:

43972

AN:

251268

Hom.:

4806

AF XY:

0.179

AC XY:

24304

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.0611

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.293

Gnomad EAS exome

AF:

0.000599

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.209

AC:

305884

AN:

1461828

Hom.:

34591

Cov.:

AF XY:

0.208

AC XY:

151078

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0602

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.297

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.166

AC:

25261

AN:

152260

Hom.:

2681

Cov.:

AF XY:

0.162

AC XY:

12039

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0661

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.226

Hom.:

5185

Bravo

AF:

0.159

TwinsUK

AF:

0.232

AC:

861

ALSPAC

AF:

0.232

AC:

896

ESP6500AA

AF:

0.0679

AC:

299

ESP6500EA

AF:

0.227

AC:

1952

ExAC

AF:

0.175

AC:

21300

Asia WGS

AF:

0.0470

AC:

166

AN:

3478

EpiCase

AF:

0.246

EpiControl

AF:

0.248

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KCTD18-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0029

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.57

.;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.10

Sift

Benign

0.60

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.020

B;B

Vest4

0.0070

MPC

0.20

ClinPred

0.0086

GERP RS

2.4

Varity_R

0.029

gMVP

0.12

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over