rs775357041

Variant names:

• chr19-50320357-T-A
• rs775357041
• NM_004977.3:c.2171-8A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-50320357-T-A
• chr19-50320357-T-C
• chr19-50320357-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004977.3(KCNC3):​c.2171-8A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNC3 NM_004977.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002572
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.2171-8A>T		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1	c.1943-8A>T		splice_region_variant, intron_variant	Intron 3 of 4		NP_001359234.1
KCNC3	NR_110912.2	n.260+236A>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNC3	ENST00000477616.2	c.2171-8A>T		splice_region_variant, intron_variant	Intron 3 of 4	1	NM_004977.3	ENSP00000434241.1
KCNC3	ENST00000670667.1	c.2170+236A>T		intron_variant	Intron 3 of 3			ENSP00000499301.1
KCNC3	ENST00000376959.6	c.2170+236A>T		intron_variant	Intron 3 of 4	5		ENSP00000366158.2
KCNC3	ENST00000474951.1	c.118+236A>T		intron_variant	Intron 2 of 3	2		ENSP00000432438.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 22074 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 153310 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81574

African (AFR) AF: 0.00 AC: 0 AN: 5218

American (AMR) AF: 0.00 AC: 0 AN: 8900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3910

East Asian (EAS) AF: 0.00 AC: 0 AN: 7686

South Asian (SAS) AF: 0.00 AC: 0 AN: 26128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 564

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 85726

Other (OTH) AF: 0.00 AC: 0 AN: 7998

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 22074 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 9864

African (AFR) AF: 0.00 AC: 0 AN: 5628

American (AMR) AF: 0.00 AC: 0 AN: 1450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 670

East Asian (EAS) AF: 0.00 AC: 0 AN: 606

South Asian (SAS) AF: 0.00 AC: 0 AN: 582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 32

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 11826

Other (OTH) AF: 0.00 AC: 0 AN: 264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.9
DANN	Benign	0.81
PhyloP100		0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0080
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: rs775357041; hg19: chr19-50823614;