7-66638281-G-T

Position:

• chr7-66638281-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP5

The NM_153033.5(KCTD7):​c.343G>T​(p.Asp115Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD7 NM_153033.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.24

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a domain BTB (size 98) in uniprot entity KCTD7_HUMAN there are 5 pathogenic changes around while only 1 benign (83%) in NM_153033.5
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-66638281-G-T is Pathogenic according to our data. Variant chr7-66638281-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 37012.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.343G>T	p.Asp115Tyr	missense_variant	3/4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.343G>T	p.Asp115Tyr	missense_variant	3/5		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.343G>T	p.Asp115Tyr	missense_variant	3/4	2	NM_153033.5	ENSP00000492240	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Progressive myoclonic epilepsy type 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.;.;.;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.72	D;D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.0	M;.;.;M;.;.
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.9	.;D;.;D;.;.
REVEL	Uncertain	0.57
Sift	Uncertain	0.015	.;D;.;D;.;.
Sift4G	Uncertain	0.019	.;D;.;D;.;.
Polyphen		0.14	B;.;.;.;.;.
Vest4		0.63, 0.62
MutPred		0.49		Gain of catalytic residue at D115 (P = 0.0148);Gain of catalytic residue at D115 (P = 0.0148);Gain of catalytic residue at D115 (P = 0.0148);Gain of catalytic residue at D115 (P = 0.0148);Gain of catalytic residue at D115 (P = 0.0148);Gain of catalytic residue at D115 (P = 0.0148);
MVP		0.90
ClinPred		0.96	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs387907262; hg19: chr7-66103268;