rs10263935

Variant names:

• chr7-66631041-G-A
• rs10263935
• NM_153033.5:c.144+1833G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153033.5(KCTD7):​c.144+1833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,032 control chromosomes in the GnomAD database, including 20,429 homozygotes. 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: 𝑓 0.51 (20429 hom., cov: 33)
• Consequence: KCTD7 NM_153033.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 22 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• 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 rank	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.144+1833G>A		intron_variant	Intron 1 of 3	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.144+1833G>A		intron_variant	Intron 1 of 4		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.144+1833G>A		intron_variant	Intron 1 of 3	2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.144+1833G>A		intron_variant	Intron 1 of 12	2		ENSP00000421074.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76870 AN: 151916 Hom.: 20400 Cov.: 33

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.482

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.506 AC: 76945 AN: 152032 Hom.: 20429 Cov.: 33 AF XY: 0.500 AC XY: 37141 AN XY: 74294

African (AFR) AF: 0.660 AC: 27353 AN: 41458

American (AMR) AF: 0.484 AC: 7393 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3472

East Asian (EAS) AF: 0.258 AC: 1336 AN: 5178

South Asian (SAS) AF: 0.361 AC: 1742 AN: 4826

European-Finnish (FIN) AF: 0.400 AC: 4217 AN: 10548

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32145 AN: 67972

Other (OTH) AF: 0.479 AC: 1012 AN: 2112

Alfa AF: 0.486 Hom.: 30602

Bravo AF: 0.518

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.87
DANN	Benign	0.65
PhyloP100		-0.14
Mutation Taster		=100/0	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: rs10263935; hg19: chr7-66096028;