rs683856

Variant names:

• chr19-50319151-T-A
• rs683856
• NM_004977.3:c.*23+1072A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-50319151-T-A
• chr19-50319151-T-C
• chr19-50319151-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004977.3(KCNC3):​c.*23+1072A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 (0 hom., cov: 30)
• Consequence: KCNC3 NM_004977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 13 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.*23+1072A>T		intron_variant	Intron 4 of 4	ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1	c.*23+1072A>T		intron_variant	Intron 4 of 4		NP_001359234.1
KCNC3	NR_110912.2	n.260+1442A>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNC3	ENST00000477616.2	c.*23+1072A>T		intron_variant	Intron 4 of 4	1	NM_004977.3	ENSP00000434241.1
KCNC3	ENST00000670667.1	c.2170+1442A>T		intron_variant	Intron 3 of 3			ENSP00000499301.1
KCNC3	ENST00000376959.6	c.2170+1442A>T		intron_variant	Intron 3 of 4	5		ENSP00000366158.2
KCNC3	ENST00000474951.1	c.118+1442A>T		intron_variant	Intron 2 of 3	2		ENSP00000432438.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151876 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151876 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74168

African (AFR) AF: 0.0000242 AC: 1 AN: 41306

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 22799

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		-0.35

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: rs683856; hg19: chr19-50822408;