7-66629140-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153033.5(KCTD7):c.76G>T(p.Asp26Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000887 in 1,533,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D26G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

KCTD7
NM_153033.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5

Conservation

PhyloP100: 5.17

Publications

1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P
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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18562734).

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.76G>T	p.Asp26Tyr	missense	Exon 1 of 4	NP_694578.1	Q96MP8-1
	KCTD7	NM_001167961.2		c.76G>T	p.Asp26Tyr	missense	Exon 1 of 5	NP_001161433.1	Q96MP8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCTD7	ENST00000639828.2	TSL:2 MANE Select	c.76G>T	p.Asp26Tyr	missense	Exon 1 of 4	ENSP00000492240.1	Q96MP8-1
KCTD7	ENST00000443322.1	TSL:1	c.76G>T	p.Asp26Tyr	missense	Exon 1 of 5	ENSP00000411624.1	Q96MP8-2
ENSG00000284461	ENST00000503687.2	TSL:2	n.76G>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000421074.1	E9PHB8

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.0000415

AC:

AN:

168536

AF XY:

0.0000427

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000526

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000912

AC:

126

AN:

1381412

Hom.:

Cov.:

AF XY:

0.0000846

AC XY:

AN XY:

685298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28638

American (AMR)

AF:

0.000115

AC:

AN:

34706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23680

East Asian (EAS)

AF:

0.00

AC:

AN:

31566

South Asian (SAS)

AF:

0.00

AC:

AN:

77132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49524

Middle Eastern (MID)

AF:

0.000363

AC:

AN:

5508

European-Non Finnish (NFE)

AF:

0.000109

AC:

117

AN:

1074086

Other (OTH)

AF:

0.0000530

AC:

AN:

56572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000658

AC:

AN:

151920

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.000131

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67952

Other (OTH)

AF:

0.000480

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000726

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000252

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Progressive myoclonic epilepsy type 3 (2)

Inborn genetic diseases (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.049

Eigen_PC

Benign

0.033

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.55

PhyloP100

5.2

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.31

REVEL

Benign

0.23

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.011

Polyphen

0.74

Vest4

0.38

MVP

0.75

ClinPred

0.26

GERP RS

4.0

PromoterAI

-0.051

Neutral

(source)

Varity_R

0.25

gMVP

0.42

Mutation Taster

=81/19

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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