chr7-66628920-C-G

Variant names:

• chr7-66628920-C-G
• rs886062409
• NM_153033.5:c.-145C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153033.5(KCTD7):​c.-145C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: KCTD7 NM_153033.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.124
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P
• progressive myoclonus epilepsy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000284461 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

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.-145C>G		5_prime_UTR	Exon 1 of 4	NP_694578.1	Q96MP8-1
	KCTD7	NM_001167961.2		c.-145C>G		5_prime_UTR	Exon 1 of 5	NP_001161433.1	Q96MP8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD7	ENST00000639828.2	TSL:2 MANE Select	c.-145C>G		5_prime_UTR	Exon 1 of 4	ENSP00000492240.1	Q96MP8-1
	KCTD7	ENST00000640385.1	TSL:5	c.-145C>G		5_prime_UTR	Exon 1 of 5	ENSP00000491193.1	A0A1W2PP71
	KCTD7	ENST00000275532.8	TSL:4	c.-145C>G		5_prime_UTR	Exon 1 of 4	ENSP00000275532.4	A0A1X7SBW1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 8

GnomAD4 genome Cov.: 30

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
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		0.12
PromoterAI		-0.13	Neutral

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: rs886062409; hg19: chr7-66093907;