rs57580125

Variant names:

• chr7-66638448-C-CAGGA
• rs57580125
• NM_153033.5:c.493+18_493+21dupAGGA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Benign. The variant received -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 VariationId 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.

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.493+18_493+21dupAGGA		intron	N/A	NP_694578.1	Q96MP8-1
	KCTD7	NM_001167961.2		c.493+18_493+21dupAGGA		intron	N/A	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.493+18_493+21dupAGGA		intron	N/A	ENSP00000492240.1	Q96MP8-1
	KCTD7	ENST00000443322.1	TSL:1	c.493+18_493+21dupAGGA		intron	N/A	ENSP00000411624.1	Q96MP8-2
	ENSG00000284461	ENST00000503687.2	TSL:2	n.323+18_323+21dupAGGA		intron	N/A	ENSP00000421074.1	E9PHB8

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

GnomAD2 exomes AF: 0.132 AC: 32889 AN: 249990 AF XY: 0.131

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 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

African (AFR) AF: 0.0803 AC: 2684 AN: 33432

American (AMR) AF: 0.101 AC: 4506 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 5488 AN: 26114

East Asian (EAS) AF: 0.268 AC: 10623 AN: 39650

South Asian (SAS) AF: 0.124 AC: 10654 AN: 86226

European-Finnish (FIN) AF: 0.232 AC: 12363 AN: 53394

Middle Eastern (MID) AF: 0.111 AC: 640 AN: 5750

European-Non Finnish (NFE) AF: 0.114 AC: 126409 AN: 1110784

Other (OTH) AF: 0.124 AC: 7468 AN: 60326

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

African (AFR) AF: 0.0811 AC: 3364 AN: 41474

American (AMR) AF: 0.107 AC: 1630 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 692 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1013 AN: 5158

South Asian (SAS) AF: 0.120 AC: 579 AN: 4822

European-Finnish (FIN) AF: 0.234 AC: 2466 AN: 10554

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 7993 AN: 67974

Other (OTH) AF: 0.124 AC: 261 AN: 2108

Alfa AF: 0.133 Hom.: 236

Bravo AF: 0.108

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Progressive myoclonic epilepsy type 3 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs57580125; hg19: chr7-66103435; COSMIC: COSV51876586; COSMIC: COSV51876586;