19-50314943-C-T

Variant names:

• chr19-50314943-C-T
• rs371995384
• NM_004977.3:c.*1172G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_004977.3(KCNC3):​c.*1172G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 302,466 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (7 hom.)
• Consequence: KCNC3 NM_004977.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0530
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.044).
• BP6: Variant 19-50314943-C-T is Benign according to our data. Variant chr19-50314943-C-T is described in ClinVar as [Benign]. Clinvar id is 3777870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000598 (91/152086) while in subpopulation SAS AF = 0.0185 (89/4818). AF 95% confidence interval is 0.0154. There are 1 homozygotes in GnomAd4. There are 69 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 91 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.*1172G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000477616.2	NP_004968.2
KCNC3	NR_110912.2	n.367G>A		non_coding_transcript_exon_variant	Exon 4 of 4
KCNC3	NM_001372305.1	c.*1172G>A		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.*1172G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_004977.3	ENSP00000434241.1
KCNC3	ENST00000670667.1	c.2218G>A	p.Val740Met	missense_variant	Exon 4 of 4			ENSP00000499301.1
KCNC3	ENST00000376959.6	c.*90G>A		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000366158.2
KCNC3	ENST00000474951.1	c.*90G>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000432438.1

Frequencies

GnomAD3 genomes AF: 0.000599 AC: 91 AN: 151968 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.0185

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00157 AC: 20 AN: 12706 AF XY: 0.00186

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: 0.00251 AC: 377 AN: 150380 Hom.: 7 Cov.: 0 AF XY: 0.00374 AC XY: 319 AN XY: 85354

African (AFR) AF: 0.00 AC: 0 AN: 1246

American (AMR) AF: 0.000205 AC: 1 AN: 4872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2984

East Asian (EAS) AF: 0.00 AC: 0 AN: 1828

South Asian (SAS) AF: 0.0101 AC: 371 AN: 36602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7776

Middle Eastern (MID) AF: 0.00192 AC: 1 AN: 522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 87528

Other (OTH) AF: 0.000570 AC: 4 AN: 7022

GnomAD4 genome AF: 0.000598 AC: 91 AN: 152086 Hom.: 1 Cov.: 31 AF XY: 0.000928 AC XY: 69 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41482

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5128

South Asian (SAS) AF: 0.0185 AC: 89 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000208 Hom.: 0

Bravo AF: 0.000132

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KCNC3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Uncertain	1.0
PhyloP100		0.053
Mutation Taster		=83/17	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs371995384; hg19: chr19-50818200;