rs368827687

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-50314910-G-A
• chr19-50314910-G-C
• chr19-50314910-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004977.3(KCNC3):​c.*1205C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000379 in 158,460 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000038 (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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.*1205C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000477616.2	NP_004968.2
KCNC3	NR_110912.2	n.400C>T		non_coding_transcript_exon_variant	Exon 4 of 4
KCNC3	NM_001372305.1	c.*1205C>T		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>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_004977.3	ENSP00000434241.1
KCNC3	ENST00000670667.1	c.2251C>T	p.Pro751Ser	missense_variant	Exon 4 of 4			ENSP00000499301.1
KCNC3	ENST00000376959.6	c.*123C>T		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000366158.2
KCNC3	ENST00000474951.1	c.*123C>T		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000432438.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.000139 AC: 2 AN: 14414 AF XY: 0.000253

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: 0.000229

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000379 AC: 6 AN: 158460 Hom.: 0 Cov.: 0 AF XY: 0.0000555 AC XY: 5 AN XY: 90054

African (AFR) AF: 0.00 AC: 0 AN: 1430

American (AMR) AF: 0.00 AC: 0 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: 0.000104 AC: 4 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: 0.0000217 AC: 2 AN: 91958

Other (OTH) AF: 0.00 AC: 0 AN: 7420

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.11
CADD	Benign	19
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;