Variant 1-215586638-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016121.5(KCTD3):c.770G>A(p.Ser257Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00185 in 1,614,064 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 5 hom. )

Consequence

KCTD3
NM_016121.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.53

Variant links:

Genes affected

KCTD3 (HGNC:21305): (potassium channel tetramerization domain containing 3) This gene encodes a member of the potassium channel tetramerization-domain containing (KCTD) protein family. Members of this protein family regulate the biophysical characteristics of ion channels. In mouse, this protein interacts with hyperpolarization-activated cyclic nucleotide-gated channel complex 3 and enhances its cell surface expression and current density. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

KCTD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009257942).

BP6

Variant 1-215586638-G-A is Benign according to our data. Variant chr1-215586638-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2218789.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 242 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD3	NM_016121.5 linkuse as main transcript	c.770G>A	p.Ser257Asn	missense_variant	9/18	ENST00000259154.9	NP_057205.2	Q9Y597-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD3	ENST00000259154.9 linkuse as main transcript	c.770G>A	p.Ser257Asn	missense_variant	9/18	1	NM_016121.5	ENSP00000259154.2		Q9Y597-1

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

242

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00231

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00157

AC:

394

AN:

251408

Hom.:

AF XY:

0.00153

AC XY:

208

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00420

Gnomad NFE exome

AF:

0.00218

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00187

AC:

2738

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

1393

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000452

Gnomad4 FIN exome

AF:

0.00462

Gnomad4 NFE exome

AF:

0.00206

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00159

AC:

242

AN:

152252

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

109

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.00231

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00119

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00160

AC:

194

EpiCase

AF:

0.00262

EpiControl

AF:

0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

KCTD3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 26, 2024

This variant is classified as likely 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

0.088

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

M_CAP

Benign

0.014

MetaRNN

Benign

0.0093

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.34

REVEL

Benign

0.10

Sift

Benign

0.13

Sift4G

Benign

0.32

Polyphen

0.029

Vest4

0.53

MVP

0.22

MPC

1.1

ClinPred

0.017

GERP RS

5.9

Varity_R

0.14

gMVP

0.40

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