19-50314910-G-C

Variant names:

• chr19-50314910-G-C
• rs368827687
• NM_004977.3:c.*1205C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_004977.3(KCNC3):​c.*1205C>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000586 in 310,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00054 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00063 (0 hom.)
• Consequence: KCNC3 NM_004977.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.91
• 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: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (REVEL=0.071).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000539 (82/152098) while in subpopulation NFE AF = 0.00104 (71/67996). AF 95% confidence interval is 0.000848. There are 0 homozygotes in GnomAd4. There are 38 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 82 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.*1205C>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000477616.2	NP_004968.2
KCNC3	NR_110912.2	n.400C>G		non_coding_transcript_exon_variant	Exon 4 of 4
KCNC3	NM_001372305.1	c.*1205C>G		3_prime_UTR_variant	Exon 5 of 5		NP_001359234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNC3	ENST00000477616.2	c.*1205C>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_004977.3	ENSP00000434241.1
KCNC3	ENST00000670667.1	c.2251C>G	p.Pro751Ala	missense_variant	Exon 4 of 4			ENSP00000499301.1
KCNC3	ENST00000376959.6	c.*123C>G		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000366158.2
KCNC3	ENST00000474951.1	c.*123C>G		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000432438.1

Frequencies

GnomAD3 genomes AF: 0.000539 AC: 82 AN: 152098 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000347 AC: 5 AN: 14414 AF XY: 0.000379

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000510

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000687

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000631 AC: 100 AN: 158460 Hom.: 0 Cov.: 0 AF XY: 0.000533 AC XY: 48 AN XY: 90054

African (AFR) AF: 0.000699 AC: 1 AN: 1430

American (AMR) AF: 0.000548 AC: 3 AN: 5474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3186

East Asian (EAS) AF: 0.00 AC: 0 AN: 2180

South Asian (SAS) AF: 0.00 AC: 0 AN: 38284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 564

European-Non Finnish (NFE) AF: 0.00103 AC: 95 AN: 91958

Other (OTH) AF: 0.000135 AC: 1 AN: 7420

GnomAD4 genome AF: 0.000539 AC: 82 AN: 152098 Hom.: 0 Cov.: 31 AF XY: 0.000512 AC XY: 38 AN XY: 74282

African (AFR) AF: 0.000193 AC: 8 AN: 41426

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Uncertain	1.0
PhyloP100		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=97/3	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368827687; hg19: chr19-50818167;