19-50314934-G-A

Variant names:

• chr19-50314934-G-A
• rs368099861
• NM_004977.3:c.*1181C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004977.3(KCNC3):​c.*1181C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNC3 NM_004977.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.113).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC3	NM_004977.3	MANE Select	c.*1181C>T		3_prime_UTR	Exon 5 of 5	NP_004968.2
	KCNC3	NM_001372305.1		c.*1181C>T		3_prime_UTR	Exon 5 of 5	NP_001359234.1
	KCNC3	NR_110912.2		n.376C>T		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC3	ENST00000477616.2	TSL:1 MANE Select	c.*1181C>T		3_prime_UTR	Exon 5 of 5	ENSP00000434241.1	Q14003
	KCNC3	ENST00000670667.1		c.2227C>T	p.Arg743Cys	missense	Exon 4 of 4	ENSP00000499301.1	A0A590UJ62
	KCNC3	ENST00000376959.6	TSL:5	c.*99C>T		3_prime_UTR	Exon 5 of 5	ENSP00000366158.2	E7ETH1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 156212 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 88546

African (AFR) AF: 0.00 AC: 0 AN: 1368

American (AMR) AF: 0.00 AC: 0 AN: 5268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3106

East Asian (EAS) AF: 0.00 AC: 0 AN: 2076

South Asian (SAS) AF: 0.00 AC: 0 AN: 37606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 546

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 90980

Other (OTH) AF: 0.00 AC: 0 AN: 7336

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Uncertain	1.0
PhyloP100		1.1
Mutation Taster		=90/10	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs368099861; hg19: chr19-50818191;