19-50319151-T-G

Variant names:

• chr19-50319151-T-G
• rs683856
• NM_004977.3:c.*23+1072A>C

Variant summary

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

The NM_004977.3(KCNC3):​c.*23+1072A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,912 control chromosomes in the GnomAD database, including 8,328 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 0.31 (8328 hom., cov: 30)
• Consequence: KCNC3 NM_004977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 13 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: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC3	NM_004977.3	MANE Select	c.*23+1072A>C		intron	N/A	NP_004968.2
	KCNC3	NM_001372305.1		c.*23+1072A>C		intron	N/A	NP_001359234.1
	KCNC3	NR_110912.2		n.260+1442A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC3	ENST00000477616.2	TSL:1 MANE Select	c.*23+1072A>C		intron	N/A	ENSP00000434241.1
	KCNC3	ENST00000670667.1		c.2170+1442A>C		intron	N/A	ENSP00000499301.1
	KCNC3	ENST00000376959.6	TSL:5	c.2170+1442A>C		intron	N/A	ENSP00000366158.2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46544 AN: 151794 Hom.: 8319 Cov.: 30

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.307 AC: 46575 AN: 151912 Hom.: 8328 Cov.: 30 AF XY: 0.312 AC XY: 23141 AN XY: 74252

African (AFR) AF: 0.204 AC: 8437 AN: 41402

American (AMR) AF: 0.342 AC: 5214 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3468

East Asian (EAS) AF: 0.864 AC: 4462 AN: 5164

South Asian (SAS) AF: 0.481 AC: 2318 AN: 4818

European-Finnish (FIN) AF: 0.274 AC: 2893 AN: 10568

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21247 AN: 67944

Other (OTH) AF: 0.297 AC: 625 AN: 2104

Alfa AF: 0.314 Hom.: 22799

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.48
PhyloP100		-0.35
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: rs683856; hg19: chr19-50822408;