rs117194263

Variant names:

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.654C>T(p.Asp218Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,614,114 control chromosomes in the GnomAD database, including 497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 61 hom., cov: 32)

Exomes 𝑓: 0.010 ( 436 hom. )

Consequence

KCTD7
NM_153033.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.357

Publications

6 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 (MetaRNN=0.0016175508).

BP6

Variant 7-66639016-C-T is Benign according to our data. Variant chr7-66639016-C-T is described in ClinVar as Benign. ClinVar VariationId is 129371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.357 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153033.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD7	NM_153033.5	MANE Select	c.654C>T	p.Asp218Asp	synonymous	Exon 4 of 4	NP_694578.1
	KCTD7	NM_001167961.2		c.654C>T	p.Asp218Asp	synonymous	Exon 4 of 5	NP_001161433.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCTD7	ENST00000639828.2	TSL:2 MANE Select	c.654C>T	p.Asp218Asp	synonymous	Exon 4 of 4	ENSP00000492240.1
KCTD7	ENST00000443322.1	TSL:1	c.654C>T	p.Asp218Asp	synonymous	Exon 4 of 5	ENSP00000411624.1
ENSG00000284461	ENST00000503687.2	TSL:2	n.397+87C>T		intron	N/A	ENSP00000421074.1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2214

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0231

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0927

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0752

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00507

Gnomad OTH

AF:

0.0192

GnomAD2 exomes

AF:

0.0218

AC:

5491

AN:

251440

AF XY:

0.0201

show subpopulations

Gnomad AFR exome

AF:

0.00301

Gnomad AMR exome

AF:

0.0384

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.0868

Gnomad FIN exome

AF:

0.0675

Gnomad NFE exome

AF:

0.00541

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0103

AC:

15019

AN:

1461884

Hom.:

436

Cov.:

AF XY:

0.0101

AC XY:

7331

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00427

AC:

143

AN:

33480

American (AMR)

AF:

0.0362

AC:

1618

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00344

AC:

AN:

26136

East Asian (EAS)

AF:

0.103

AC:

4092

AN:

39700

South Asian (SAS)

AF:

0.00929

AC:

801

AN:

86256

European-Finnish (FIN)

AF:

0.0691

AC:

3692

AN:

53416

Middle Eastern (MID)

AF:

0.00902

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00322

AC:

3580

AN:

1112008

Other (OTH)

AF:

0.0157

AC:

951

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

949

1899

2848

3798

4747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0146

AC:

2227

AN:

152230

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1323

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00325

AC:

135

AN:

41552

American (AMR)

AF:

0.0233

AC:

356

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3466

East Asian (EAS)

AF:

0.0928

AC:

480

AN:

5174

South Asian (SAS)

AF:

0.0110

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0752

AC:

796

AN:

10586

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00507

AC:

345

AN:

68018

Other (OTH)

AF:

0.0232

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00592

Hom.:

Bravo

AF:

0.0106

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.0202

AC:

2456

Asia WGS

AF:

0.0720

AC:

248

AN:

3478

EpiCase

AF:

0.00338

EpiControl

AF:

0.00338

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Progressive myoclonic epilepsy type 3 (2)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_noAF

Benign

-0.42

CADD

Benign

2.9

(source)

DANN

Benign

0.67

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0016

PhyloP100

-0.36

GERP RS

-2.7

PromoterAI

0.0046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over