ENST00000503687.2:n.-46C>A

Variant names:

• chr7-66628912-G-A
• rs1786372876
• NM_153033.5:c.-153G>A

Variant summary

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

The ENST00000503687.2(ENSG00000284461):​n.-153G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 539,902 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000019 (0 hom.)
• Consequence: ENSG00000284461 ENST00000503687.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• 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=-0.61).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.-153G>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.-153G>A		5_prime_UTR_variant	Exon 1 of 5		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.-153G>A		5_prime_UTR_variant	Exon 1 of 4	2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.-153G>A		upstream_gene_variant		2		ENSP00000421074.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000185 AC: 1 AN: 539902 Hom.: 0 Cov.: 8 AF XY: 0.00000365 AC XY: 1 AN XY: 274210

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11036

American (AMR) AF: 0.00 AC: 0 AN: 6964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10394

East Asian (EAS) AF: 0.00 AC: 0 AN: 21348

South Asian (SAS) AF: 0.00 AC: 0 AN: 25640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1838

European-Non Finnish (NFE) AF: 0.00000243 AC: 1 AN: 411732

Other (OTH) AF: 0.00 AC: 0 AN: 25868

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		-0.35
PromoterAI		-0.023	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: rs1786372876; hg19: chr7-66093899;