19-50320577-AG-A

Variant names:

• chr19-50320577-AG-A
• rs757630847
• NM_004977.3:c.2170+15delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004977.3(KCNC3):​c.2170+15delC variant causes a intron change. The variant allele was found at a frequency of 0.0000206 in 1,603,860 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: KCNC3 NM_004977.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.78
• Publications: 0 publications found

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]

KCNC3 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 13

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-50320577-AG-A is Benign according to our data. Variant chr19-50320577-AG-A is described in ClinVar as Benign. ClinVar VariationId is 3012353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00002 (3/149744) while in subpopulation EAS AF = 0.000405 (2/4940). AF 95% confidence interval is 0.0000714. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 30 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004977.3. 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
	KCNC3	NM_004977.3	MANE Select	c.2170+15delC		intron	N/A	NP_004968.2
	KCNC3	NM_001372305.1		c.1942+15delC		intron	N/A	NP_001359234.1
	KCNC3	NR_110912.2		n.260+15delC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC3	ENST00000477616.2	TSL:1 MANE Select	c.2170+15delC		intron	N/A	ENSP00000434241.1	Q14003
	KCNC3	ENST00000670667.1		c.2170+15delC		intron	N/A	ENSP00000499301.1	A0A590UJ62
	KCNC3	ENST00000376959.6	TSL:5	c.2170+15delC		intron	N/A	ENSP00000366158.2	E7ETH1

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 149744 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000405

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000167 AC: 4 AN: 239336 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000206 AC: 30 AN: 1454116 Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15 AN XY: 723164

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 43998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4418

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1108484

Other (OTH) AF: 0.00 AC: 0 AN: 60008

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 149744 Hom.: 0 Cov.: 30 AF XY: 0.0000137 AC XY: 1 AN XY: 73074

African (AFR) AF: 0.00 AC: 0 AN: 40544

American (AMR) AF: 0.00 AC: 0 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.000405 AC: 2 AN: 4940

South Asian (SAS) AF: 0.00 AC: 0 AN: 4684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67364

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

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: rs757630847; hg19: chr19-50823834; COSMIC: COSV65387077;