Variant 2-200490143-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152387.4(KCTD18):c.1238C>T(p.Ala413Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,606,550 control chromosomes in the GnomAD database, including 160 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 96 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 64 hom. )

Consequence

KCTD18
NM_152387.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.191

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022561848).

BP6

Variant 2-200490143-G-A is Benign according to our data. Variant chr2-200490143-G-A is described in ClinVar as [Benign]. Clinvar id is 775804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0628 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.1238C>T	p.Ala413Val	missense_variant	7/7	ENST00000359878.8	NP_689600.2	Q6PI47-1
KCTD18	NM_001321547.2 linkuse as main transcript	c.1238C>T	p.Ala413Val	missense_variant	7/7		NP_001308476.1	Q6PI47-1A8K4A2
KCTD18	NM_001321548.2 linkuse as main transcript	c.611C>T	p.Ala204Val	missense_variant	7/7		NP_001308477.1
KCTD18	NM_001321550.2 linkuse as main transcript	c.611C>T	p.Ala204Val	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.1238C>T	p.Ala413Val	missense_variant	7/7	1	NM_152387.4	ENSP00000352941.3		Q6PI47-1
KCTD18	ENST00000409157.5 linkuse as main transcript	c.1238C>T	p.Ala413Val	missense_variant	7/7	1		ENSP00000386751.1		Q6PI47-1

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2925

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0647

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00514

AC:

1279

AN:

248916

Hom.:

AF XY:

0.00396

AC XY:

533

AN XY:

134486

show subpopulations

Gnomad AFR exome

AF:

0.0675

Gnomad AMR exome

AF:

0.00433

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000989

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.00362

GnomAD4 exome

AF:

0.00179

AC:

2598

AN:

1454178

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1096

AN XY:

721728

show subpopulations

Gnomad4 AFR exome

AF:

0.0600

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.00385

GnomAD4 genome

AF:

0.0193

AC:

2939

AN:

152372

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1387

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0648

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00235

Hom.:

Bravo

AF:

0.0213

ESP6500AA

AF:

0.0631

AC:

278

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00641

AC:

778

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

KCTD18-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 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

0.079

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.7

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0020

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.49

.;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.54

N;N

REVEL

Benign

0.041

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.20

T;T

Polyphen

0.0080

B;B

Vest4

0.035

MVP

0.38

MPC

0.20

ClinPred

0.0089

GERP RS

1.1

Varity_R

0.029

gMVP

0.17

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