rs1555781806

Positions:

• chr19-50329070-CTG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PP5_Moderate

The NM_004977.3(KCNC3):​c.11_12del​(p.Ser4CysfsTer96) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNC3 NM_004977.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.17

Genes affected

KCNC3 (HGNC:6235): (potassium voltage-gated channel subfamily C member 3) The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to one of these subfamilies, namely the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. Alternate splicing results in several transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 7 pathogenic variants in the truncated region.
• PP5: Variant 19-50329070-CTG-C is Pathogenic according to our data. Variant chr19-50329070-CTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 522615.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.11_12del	p.Ser4CysfsTer96	frameshift_variant	1/5	ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1			5_prime_UTR_variant	1/5		NP_001359234.1
KCNC3	NR_110912.2	n.68+4397_68+4398del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNC3	ENST00000477616.2	c.11_12del	p.Ser4CysfsTer96	frameshift_variant	1/5	1	NM_004977.3	ENSP00000434241
KCNC3	ENST00000376959.6	c.11_12del	p.Ser4CysfsTer96	frameshift_variant	1/5	5		ENSP00000366158	A2
KCNC3	ENST00000670667.1	c.11_12del	p.Ser4CysfsTer96	frameshift_variant	1/4			ENSP00000499301	P3
KCNC3	ENST00000474951.1	c.-75+4397_-75+4398del		intron_variant		2		ENSP00000432438

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000182 AC: 2 AN: 1096650 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 538260

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000804

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spinocerebellar ataxia type 13 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Dec 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

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: rs1555781806; hg19: chr19-50832327;