rs1554300943

Variant names:

• chr7-66639039-G-C
• rs1554300943
• NM_153033.5:c.677G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153033.5(KCTD7):​c.677G>C​(p.Cys226Ser) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD7 NM_153033.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.24
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153033.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD7	NM_153033.5	MANE Select	c.677G>C	p.Cys226Ser	missense	Exon 4 of 4	NP_694578.1
	KCTD7	NM_001167961.2		c.677G>C	p.Cys226Ser	missense	Exon 4 of 5	NP_001161433.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD7	ENST00000639828.2	TSL:2 MANE Select	c.677G>C	p.Cys226Ser	missense	Exon 4 of 4	ENSP00000492240.1
	KCTD7	ENST00000443322.1	TSL:1	c.677G>C	p.Cys226Ser	missense	Exon 4 of 5	ENSP00000411624.1
	ENSG00000284461	ENST00000503687.2	TSL:2	n.397+110G>C		intron	N/A	ENSP00000421074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Progressive myoclonic epilepsy type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	25
DANN	Benign	0.91
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.4	L
PhyloP100		9.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.55
Sift	Benign	0.20	T
Sift4G	Uncertain	0.011	D
Polyphen		0.98	D
Vest4		0.93
MutPred		0.47		Gain of disorder (P = 7e-04)
MVP		0.93
ClinPred		0.75	D
GERP RS		5.7
PromoterAI		0.0050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.76
Mutation Taster		=23/77	disease causing

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: rs1554300943; hg19: chr7-66104026;