rs3764904

Variant names:

• chr7-66633397-G-A
• rs3764904
• NM_153033.5:c.267G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-66633397-G-A
• chr7-66633397-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_153033.5(KCTD7):​c.267G>A​(p.Thr89Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,613,866 control chromosomes in the GnomAD database, including 10,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (749 hom., cov: 31)
  • Exomes 𝑓: 0.11 (9815 hom.)
• Consequence: KCTD7 NM_153033.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -3.69
• Publications: 15 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 7-66633397-G-A is Benign according to our data. Variant chr7-66633397-G-A is described in ClinVar as Benign. ClinVar VariationId is 129370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD7	NM_153033.5	MANE Select	c.267G>A	p.Thr89Thr	synonymous	Exon 2 of 4	NP_694578.1
	KCTD7	NM_001167961.2		c.267G>A	p.Thr89Thr	synonymous	Exon 2 of 5	NP_001161433.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD7	ENST00000639828.2	TSL:2 MANE Select	c.267G>A	p.Thr89Thr	synonymous	Exon 2 of 4	ENSP00000492240.1
	KCTD7	ENST00000443322.1	TSL:1	c.267G>A	p.Thr89Thr	synonymous	Exon 2 of 5	ENSP00000411624.1
	ENSG00000284461	ENST00000503687.2	TSL:2	n.144+4189G>A		intron	N/A	ENSP00000421074.1

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13353 AN: 152000 Hom.: 748 Cov.: 31

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0876

GnomAD2 exomes AF: 0.104 AC: 26260 AN: 251454 AF XY: 0.107

Gnomad AFR exome AF: 0.0186

Gnomad AMR exome AF: 0.0618

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.0899

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.111 AC: 162386 AN: 1461748 Hom.: 9815 Cov.: 33 AF XY: 0.111 AC XY: 81032 AN XY: 727182

African (AFR) AF: 0.0166 AC: 557 AN: 33476

American (AMR) AF: 0.0629 AC: 2813 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5341 AN: 26134

East Asian (EAS) AF: 0.165 AC: 6549 AN: 39696

South Asian (SAS) AF: 0.101 AC: 8670 AN: 86252

European-Finnish (FIN) AF: 0.163 AC: 8687 AN: 53416

Middle Eastern (MID) AF: 0.0954 AC: 550 AN: 5764

European-Non Finnish (NFE) AF: 0.111 AC: 122941 AN: 1111900

Other (OTH) AF: 0.104 AC: 6278 AN: 60386

GnomAD4 genome AF: 0.0878 AC: 13354 AN: 152118 Hom.: 749 Cov.: 31 AF XY: 0.0902 AC XY: 6706 AN XY: 74370

African (AFR) AF: 0.0208 AC: 862 AN: 41510

American (AMR) AF: 0.0761 AC: 1162 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3468

East Asian (EAS) AF: 0.104 AC: 538 AN: 5158

South Asian (SAS) AF: 0.0976 AC: 470 AN: 4816

European-Finnish (FIN) AF: 0.160 AC: 1695 AN: 10572

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7649 AN: 68006

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.104 Hom.: 573

Bravo AF: 0.0789

Asia WGS AF: 0.0900 AC: 312 AN: 3478

EpiCase AF: 0.107

EpiControl AF: 0.108

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Progressive myoclonic epilepsy type 3 (3)
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		-3.7
Mutation Taster		=99/1	polymorphism (auto)

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: rs3764904; hg19: chr7-66098384; COSMIC: COSV51876813;