rs387907262

Variant names:

• chr7-66638281-G-A
• rs387907262
• NM_153033.5:c.343G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1 PM2 PM5

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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D115Y) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD7 NM_153033.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.24
• Publications: 6 publications found

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: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• progressive myoclonus epilepsy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000284461 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM1: In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_153033.5
• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: 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 rank	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.343G>A	p.Asp115Asn	missense_variant	Exon 3 of 4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.343G>A	p.Asp115Asn	missense_variant	Exon 3 of 5		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.343G>A	p.Asp115Asn	missense_variant	Exon 3 of 4	2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.173G>A		non_coding_transcript_exon_variant	Exon 2 of 13	2		ENSP00000421074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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;.;.
PhyloP100		9.2
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
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs387907262; hg19: chr7-66103268;