Variant 7-66638322-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_153033.5(KCTD7):c.384G>C(p.Glu128Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E128E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KCTD7
NM_153033.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

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 Likely_pathogenic. Variant got 8 ACMG points.

PM1

In a domain BTB (size 98) in uniprot entity KCTD7_HUMAN there are 16 pathogenic changes around while only 2 benign (89%) in NM_153033.5

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD7	NM_153033.5 linkuse as main transcript	c.384G>C	p.Glu128Asp	missense_variant	3/4	ENST00000639828.2
KCTD7	NM_001167961.2 linkuse as main transcript	c.384G>C	p.Glu128Asp	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD7	ENST00000639828.2 linkuse as main transcript	c.384G>C	p.Glu128Asp	missense_variant	3/4	2	NM_153033.5	A1	Q96MP8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251490

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.77

D;.;.;.;.;.

Eigen

Benign

0.057

Eigen_PC

Benign

0.078

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

D;D;D;D;D;D

M_CAP

Benign

0.061

MetaRNN

Pathogenic

0.95

D;D;D;D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.6

M;.;.;M;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

Polyphen

0.99

D;.;.;.;.;.

Vest4

0.97, 0.97

MutPred

0.91

Loss of methylation at K127 (P = 0.1292);Loss of methylation at K127 (P = 0.1292);Loss of methylation at K127 (P = 0.1292);Loss of methylation at K127 (P = 0.1292);Loss of methylation at K127 (P = 0.1292);Loss of methylation at K127 (P = 0.1292);

MVP

0.88

ClinPred

0.97

GERP RS

3.8

Varity_R

0.53

gMVP

0.93

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