chr19-50320323-G-C

Variant names:

• chr19-50320323-G-C
• rs756181510
• NM_004977.3:c.2197C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004977.3(KCNC3):​c.2197C>G​(p.Gln733Glu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q733K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNC3 NM_004977.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08668229).

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.2197C>G	p.Gln733Glu	missense	Exon 4 of 5	NP_004968.2
	KCNC3	NM_001372305.1		c.1969C>G	p.Gln657Glu	missense	Exon 4 of 5	NP_001359234.1
	KCNC3	NR_110912.2		n.260+270C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC3	ENST00000477616.2	TSL:1 MANE Select	c.2197C>G	p.Gln733Glu	missense	Exon 4 of 5	ENSP00000434241.1	Q14003
	KCNC3	ENST00000670667.1		c.2170+270C>G		intron	N/A	ENSP00000499301.1	A0A590UJ62
	KCNC3	ENST00000376959.6	TSL:5	c.2170+270C>G		intron	N/A	ENSP00000366158.2	E7ETH1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 346118 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 177576

African (AFR) AF: 0.00 AC: 0 AN: 9640

American (AMR) AF: 0.00 AC: 0 AN: 12974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8230

East Asian (EAS) AF: 0.00 AC: 0 AN: 15446

South Asian (SAS) AF: 0.00 AC: 0 AN: 37838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 225910

Other (OTH) AF: 0.00 AC: 0 AN: 17326

GnomAD4 genome Cov.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	0.0093	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.23
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.33	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.10	N
REVEL	Uncertain	0.38
Sift	Benign	1.0	T
Sift4G	Benign	0.54	T
Polyphen		0.0020	B
Vest4		0.099
MutPred		0.069		Gain of glycosylation at P732 (P = 0.0871)
MVP		0.63
ClinPred		0.052	T
GERP RS		2.3
Varity_R		0.044
gMVP		0.10
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs756181510; hg19: chr19-50823580;