rs3764904

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_153033.5(KCTD7):c.267G>A(p.Thr89Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,613,866 control chromosomes in the GnomAD database, including 10,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 749 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9815 hom. )

Consequence

KCTD7
NM_153033.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -3.69

Publications

15 publications found

Variant links:

Genes affected

KCTD7 (HGNC:21957): (potassium channel tetramerization domain containing 7) This gene encodes a member of the potassium channel tetramerization domain-containing protein family. Family members are identified on a structural basis and contain an amino-terminal domain similar to the T1 domain present in the voltage-gated potassium channel. Mutations in this gene have been associated with progressive myoclonic epilepsy-3. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

KCTD7 Gene-Disease associations (from GenCC):

progressive myoclonic epilepsy type 3
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
progressive myoclonus epilepsy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

KCTD7 links:

ENSG00000284461 (HGNC:):

ENSG00000284461 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 7-66633397-G-A is Benign according to our data. Variant chr7-66633397-G-A is described in ClinVar as [Benign]. Clinvar id is 129370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD7	NM_153033.5 link	c.267G>A	p.Thr89Thr	synonymous_variant	Exon 2 of 4	ENST00000639828.2	NP_694578.1	Q96MP8-1A0A024RDN7
KCTD7	NM_001167961.2 link	c.267G>A	p.Thr89Thr	synonymous_variant	Exon 2 of 5		NP_001161433.1	Q96MP8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2 link	c.267G>A	p.Thr89Thr	synonymous_variant	Exon 2 of 4	2	NM_153033.5	ENSP00000492240.1		Q96MP8-1
ENSG00000284461	ENST00000503687.2 link	n.144+4189G>A		intron_variant	Intron 1 of 12	2		ENSP00000421074.1		E9PHB8

Frequencies

GnomAD3 genomes

AF:

0.0878

AC:

13353

AN:

152000

Hom.:

748

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0208

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0763

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.0975

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0876

GnomAD2 exomes

AF:

0.104

AC:

26260

AN:

251454

AF XY:

0.107

show subpopulations

Gnomad AFR exome

AF:

0.0186

Gnomad AMR exome

AF:

0.0618

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.0899

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.111

AC:

162386

AN:

1461748

Hom.:

9815

Cov.:

AF XY:

0.111

AC XY:

81032

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.0166

AC:

557

AN:

33476

American (AMR)

AF:

0.0629

AC:

2813

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

5341

AN:

26134

East Asian (EAS)

AF:

0.165

AC:

6549

AN:

39696

South Asian (SAS)

AF:

0.101

AC:

8670

AN:

86252

European-Finnish (FIN)

AF:

0.163

AC:

8687

AN:

53416

Middle Eastern (MID)

AF:

0.0954

AC:

550

AN:

5764

European-Non Finnish (NFE)

AF:

0.111

AC:

122941

AN:

1111900

Other (OTH)

AF:

0.104

AC:

6278

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

7975

15950

23925

31900

39875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0878

AC:

13354

AN:

152118

Hom.:

749

Cov.:

AF XY:

0.0902

AC XY:

6706

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0208

AC:

862

AN:

41510

American (AMR)

AF:

0.0761

AC:

1162

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

672

AN:

3468

East Asian (EAS)

AF:

0.104

AC:

538

AN:

5158

South Asian (SAS)

AF:

0.0976

AC:

470

AN:

4816

European-Finnish (FIN)

AF:

0.160

AC:

1695

AN:

10572

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7649

AN:

68006

Other (OTH)

AF:

0.0890

AC:

188

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

605

1210

1816

2421

3026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.104

Hom.:

573

Bravo

AF:

0.0789

Asia WGS

AF:

0.0900

AC:

312

AN:

3478

EpiCase

AF:

0.107

EpiControl

AF:

0.108

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Nov 07, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 06, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Progressive myoclonic epilepsy type 3

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Dec 16, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Inborn genetic diseases

Benign:1

Feb 25, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.0

(source)

DANN

Benign

0.73

PhyloP100

-3.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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rs3764904

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over