NM_153033.5:c.-46C>G

Variant names:

• chr7-66629019-C-G
• rs886062412
• NM_153033.5:c.-46C>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.-46C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000302 in 1,325,010 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: KCTD7 NM_153033.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0240
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp, Ambry Genetics
• 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=-0.71).

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.-46C>G		5_prime_UTR	Exon 1 of 4	NP_694578.1	Q96MP8-1
	KCTD7	NM_001167961.2		c.-46C>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.-46C>G		5_prime_UTR	Exon 1 of 4	ENSP00000492240.1	Q96MP8-1
	KCTD7	ENST00000443322.1	TSL:1	c.-46C>G		5_prime_UTR	Exon 1 of 5	ENSP00000411624.1	Q96MP8-2
	ENSG00000284461	ENST00000503687.2	TSL:2	n.-46C>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000421074.1	E9PHB8

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000316 AC: 3 AN: 95064 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000305

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000302 AC: 4 AN: 1325010 Hom.: 0 Cov.: 28 AF XY: 0.00000153 AC XY: 1 AN XY: 653580

African (AFR) AF: 0.00 AC: 0 AN: 26702

American (AMR) AF: 0.0000722 AC: 2 AN: 27704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22726

East Asian (EAS) AF: 0.00 AC: 0 AN: 27828

South Asian (SAS) AF: 0.00 AC: 0 AN: 73300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4564

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1042956

Other (OTH) AF: 0.00 AC: 0 AN: 54060

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

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	-0.71
CADD	Benign	9.7
DANN	Benign	0.62
PhyloP100		0.024
PromoterAI		0.16	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: rs886062412; hg19: chr7-66094006;