19-50314910-G-T

Variant names:

• chr19-50314910-G-T
• rs368827687
• NM_004977.3:c.*1205C>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.*1205C>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00139 in 310,674 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: KCNC3 NM_004977.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.175).
• BP6: Variant 19-50314910-G-T is Benign according to our data. Variant chr19-50314910-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2498794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00274 (417/152214) while in subpopulation AFR AF = 0.00919 (382/41546). AF 95% confidence interval is 0.00843. There are 0 homozygotes in GnomAd4. There are 208 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 417 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.*1205C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000477616.2	NP_004968.2
KCNC3	NR_110912.2	n.400C>A		non_coding_transcript_exon_variant	Exon 4 of 4
KCNC3	NM_001372305.1	c.*1205C>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.*1205C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_004977.3	ENSP00000434241.1
KCNC3	ENST00000670667.1	c.2251C>A	p.Pro751Thr	missense_variant	Exon 4 of 4			ENSP00000499301.1
KCNC3	ENST00000376959.6	c.*123C>A		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000366158.2
KCNC3	ENST00000474951.1	c.*123C>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000432438.1

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 417 AN: 152096 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00922

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000347 AC: 5 AN: 14414 AF XY: 0.000505

Gnomad AFR exome AF: 0.00501

Gnomad AMR exome AF: 0.000255

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: 0.0000884 AC: 14 AN: 158460 Hom.: 0 Cov.: 0 AF XY: 0.0000888 AC XY: 8 AN XY: 90054

African (AFR) AF: 0.00350 AC: 5 AN: 1430

American (AMR) AF: 0.00110 AC: 6 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: 0.00 AC: 0 AN: 91958

Other (OTH) AF: 0.000404 AC: 3 AN: 7420

GnomAD4 genome AF: 0.00274 AC: 417 AN: 152214 Hom.: 0 Cov.: 31 AF XY: 0.00280 AC XY: 208 AN XY: 74410

African (AFR) AF: 0.00919 AC: 382 AN: 41546

American (AMR) AF: 0.00176 AC: 27 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67988

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00318

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KCNC3: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Uncertain	0.99
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;