NM_004977.3:c.2170+14C>G

Variant names:

• chr19-50320579-G-C
• rs189018316
• NM_004977.3:c.2170+14C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004977.3(KCNC3):​c.2170+14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,608,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: KCNC3 NM_004977.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0880
• Publications: 3 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, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-50320579-G-C is Benign according to our data. Variant chr19-50320579-G-C is described in ClinVar as Benign. ClinVar VariationId is 1573154.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000803 (122/151916) while in subpopulation AFR AF = 0.00268 (111/41430). AF 95% confidence interval is 0.00227. There are 0 homozygotes in GnomAd4. There are 48 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 122 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+14C>G		intron	N/A	NP_004968.2
	KCNC3	NM_001372305.1		c.1942+14C>G		intron	N/A	NP_001359234.1
	KCNC3	NR_110912.2		n.260+14C>G		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+14C>G		intron	N/A	ENSP00000434241.1	Q14003
	KCNC3	ENST00000670667.1		c.2170+14C>G		intron	N/A	ENSP00000499301.1	A0A590UJ62
	KCNC3	ENST00000376959.6	TSL:5	c.2170+14C>G		intron	N/A	ENSP00000366158.2	E7ETH1

Frequencies

GnomAD3 genomes AF: 0.000777 AC: 118 AN: 151800 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000782

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000257 AC: 62 AN: 241046 AF XY: 0.000245

Gnomad AFR exome AF: 0.00241

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000390

Gnomad FIN exome AF: 0.0000494

Gnomad NFE exome AF: 0.000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000109 AC: 159 AN: 1456530 Hom.: 0 Cov.: 32 AF XY: 0.000106 AC XY: 77 AN XY: 724326

African (AFR) AF: 0.00228 AC: 76 AN: 33382

American (AMR) AF: 0.000159 AC: 7 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.000429 AC: 17 AN: 39604

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85612

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4444

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1110164

Other (OTH) AF: 0.000166 AC: 10 AN: 60126

GnomAD4 genome AF: 0.000803 AC: 122 AN: 151916 Hom.: 0 Cov.: 29 AF XY: 0.000646 AC XY: 48 AN XY: 74246

African (AFR) AF: 0.00268 AC: 111 AN: 41430

American (AMR) AF: 0.000262 AC: 4 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000783 AC: 4 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67914

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.0000723 Hom.: 2

Bravo AF: 0.00101

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		0.088
Mutation Taster		=100/0	polymorphism

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: rs189018316; hg19: chr19-50823836;