rs57580125

Positions:

• chr7-66638448-C-CAGGA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_153033.5(KCTD7):​c.493+18_493+21dupAGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,612,412 control chromosomes in the GnomAD database, including 13,706 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1236 hom., cov: 30)
  • Exomes 𝑓: 0.12 (12470 hom.)
• Consequence: KCTD7 NM_153033.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.11

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]

ENSG00000284461 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 7-66638448-C-CAGGA is Benign according to our data. Variant chr7-66638448-C-CAGGA is described in ClinVar as [Benign]. Clinvar id is 262690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.493+18_493+21dupAGGA		intron_variant		ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.493+18_493+21dupAGGA		intron_variant			NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.493+18_493+21dupAGGA		intron_variant		2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.323+18_323+21dupAGGA		intron_variant		2		ENSP00000421074.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18092 AN: 151934 Hom.: 1230 Cov.: 30

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.118

GnomAD3 exomes AF: 0.132 AC: 32889 AN: 249990 Hom.: 2429 AF XY: 0.131 AC XY: 17772 AN XY: 135150

Gnomad AFR exome AF: 0.0767

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.176

Gnomad SAS exome AF: 0.123

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.124 AC: 180835 AN: 1460360 Hom.: 12470 Cov.: 32 AF XY: 0.124 AC XY: 90182 AN XY: 726232

Gnomad4 AFR exome AF: 0.0803

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.119 AC: 18117 AN: 152052 Hom.: 1236 Cov.: 30 AF XY: 0.124 AC XY: 9242 AN XY: 74306

Gnomad4 AFR AF: 0.0811

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.124

Alfa AF: 0.133 Hom.: 236

Bravo AF: 0.108

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, flagged submission	clinical testing	GeneDx	Jan 29, 2014	The variant is found in EPILEPSY,INFANT-EPI panel(s). -

Progressive myoclonic epilepsy type 3 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2016	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 16, 2017	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57580125; hg19: chr7-66103435;