ENST00000503687.2:n.-94C>T

Variant names:

• chr7-66628864-C-T
• NM_153033.5:c.-201C>T

Variant summary

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

The ENST00000503687.2(ENSG00000284461):​n.-201C>T variant causes a upstream gene 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000284461 ENST00000503687.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• 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: 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=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.-201C>T		upstream_gene_variant		ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.-201C>T		upstream_gene_variant			NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.-201C>T		upstream_gene_variant		2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.-201C>T		upstream_gene_variant		2		ENSP00000421074.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 207724 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 107054

African (AFR) AF: 0.00 AC: 0 AN: 4964

American (AMR) AF: 0.00 AC: 0 AN: 4880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6360

East Asian (EAS) AF: 0.00 AC: 0 AN: 15418

South Asian (SAS) AF: 0.00 AC: 0 AN: 6600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 924

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 139018

Other (OTH) AF: 0.00 AC: 0 AN: 12414

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		-0.30
PromoterAI		-0.17	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr7-66093851;