7-66629021-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153033.5(KCTD7):c.-44C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,475,286 control chromosomes in the GnomAD database, including 165,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20334 hom., cov: 31)
  • Exomes 𝑓: 0.46 (144781 hom.)
• Consequence: KCTD7 NM_153033.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.106

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 7-66629021-C-T is Benign according to our data. Variant chr7-66629021-C-T is described in ClinVar as [Benign]. Clinvar id is 360584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD7	NM_153033.5	c.-44C>T		5_prime_UTR_variant	1/4	ENST00000639828.2
KCTD7	NM_001167961.2	c.-44C>T		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD7	ENST00000639828.2	c.-44C>T		5_prime_UTR_variant	1/4	2	NM_153033.5	A1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76568 AN: 151462 Hom.: 20306 Cov.: 31

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.482

GnomAD3 exomes AF: 0.429 AC: 40765 AN: 94916 Hom.: 8971 AF XY: 0.424 AC XY: 22512 AN XY: 53082

Gnomad AFR exome AF: 0.690

Gnomad AMR exome AF: 0.456

Gnomad ASJ exome AF: 0.361

Gnomad EAS exome AF: 0.284

Gnomad SAS exome AF: 0.375

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.462 AC: 612215 AN: 1323718 Hom.: 144781 Cov.: 32 AF XY: 0.458 AC XY: 299366 AN XY: 652930

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.506 AC: 76639 AN: 151568 Hom.: 20334 Cov.: 31 AF XY: 0.499 AC XY: 36984 AN XY: 74072

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.479

Alfa AF: 0.489 Hom.: 2292

Bravo AF: 0.518

Asia WGS AF: 0.317 AC: 1078 AN: 3398

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Progressive myoclonic epilepsy type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	14
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs35526611; hg19: chr7-66094008;