Variant rs371919994 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_153033.5(KCTD7):c.76G>C(p.Asp26His) variant causes a missense change. The variant allele was found at a frequency of 0.000000724 in 1,381,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

KCTD7
NM_153033.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.17

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a chain BTB/POZ domain-containing protein KCTD7 (size 288) in uniprot entity KCTD7_HUMAN there are 7 pathogenic changes around while only 2 benign (78%) in NM_153033.5

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19646025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD7	NM_153033.5 linkuse as main transcript	c.76G>C	p.Asp26His	missense_variant	1/4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2 linkuse as main transcript	c.76G>C	p.Asp26His	missense_variant	1/5		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2 linkuse as main transcript	c.76G>C	p.Asp26His	missense_variant	1/4	2	NM_153033.5	ENSP00000492240	A1	Q96MP8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000593

AC:

AN:

168536

Hom.:

AF XY:

0.00

AC XY:

AN XY:

93724

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1381412

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.31e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000840

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;.;.;.;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.85

T;T;T;T;T;T

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.20

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

N;.;.;N;.;.

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

0.010

.;N;.;N;.;.

REVEL

Benign

0.089

Sift

Uncertain

0.0080

.;D;.;D;.;.

Sift4G

Uncertain

0.022

.;D;.;D;.;.

Polyphen

0.0030

B;.;.;.;.;.

Vest4

0.27, 0.31

MutPred

0.24

Gain of catalytic residue at L28 (P = 0.0862);Gain of catalytic residue at L28 (P = 0.0862);Gain of catalytic residue at L28 (P = 0.0862);Gain of catalytic residue at L28 (P = 0.0862);Gain of catalytic residue at L28 (P = 0.0862);Gain of catalytic residue at L28 (P = 0.0862);

MVP

0.69

ClinPred

0.46

GERP RS

4.0

Varity_R

0.23

gMVP

0.33

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over