rs387907262

Positions:

• chr7-66638281-G-A
• chr7-66638281-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_153033.5(KCTD7):​c.343G>A​(p.Asp115Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD7 NM_153033.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 4 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.343G>A	p.Asp115Asn	missense_variant	3/4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.343G>A	p.Asp115Asn	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>A	p.Asp115Asn	missense_variant	3/4	2	NM_153033.5	ENSP00000492240	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;.;.;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.4	L;.;.;L;.;.
MutationTaster	Benign	0.94	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.1	.;N;.;N;.;.
REVEL	Uncertain	0.30
Sift	Benign	0.079	.;T;.;T;.;.
Sift4G	Benign	0.19	.;T;.;T;.;.
Polyphen		0.030	B;.;.;.;.;.
Vest4		0.40, 0.39
MutPred		0.38		Gain of catalytic residue at D115 (P = 0.0082);Gain of catalytic residue at D115 (P = 0.0082);Gain of catalytic residue at D115 (P = 0.0082);Gain of catalytic residue at D115 (P = 0.0082);Gain of catalytic residue at D115 (P = 0.0082);Gain of catalytic residue at D115 (P = 0.0082);
MVP		0.93
ClinPred		0.72	D
GERP RS		5.6
Varity_R		0.19
gMVP		0.42

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

Other links and lift over

dbSNP: rs387907262; hg19: chr7-66103268;