rs78285067

Variant names:

• chr19-50320374-G-T
• rs78285067
• NM_004977.3:c.2171-25C>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.2171-25C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (9 hom., cov: 18)
  • Exomes 𝑓: 0.00084 (2 hom.)
• Consequence: KCNC3 NM_004977.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15
• 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 (BayesDel_noAF=-0.41).
• BP6: Variant 19-50320374-G-T is Benign according to our data. Variant chr19-50320374-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1344938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00552 (752/136282) while in subpopulation AFR AF = 0.0194 (711/36556). AF 95% confidence interval is 0.0183. There are 9 homozygotes in GnomAd4. There are 354 alleles in the male GnomAd4 subpopulation. Median coverage is 18. This position passed quality control check.
• BS2: High AC in GnomAd4 at 752 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.2171-25C>A		intron_variant	Intron 3 of 4	ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1	c.1943-25C>A		intron_variant	Intron 3 of 4		NP_001359234.1
KCNC3	NR_110912.2	n.260+219C>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNC3	ENST00000477616.2	c.2171-25C>A		intron_variant	Intron 3 of 4	1	NM_004977.3	ENSP00000434241.1
KCNC3	ENST00000670667.1	c.2170+219C>A		intron_variant	Intron 3 of 3			ENSP00000499301.1
KCNC3	ENST00000376959.6	c.2170+219C>A		intron_variant	Intron 3 of 4	5		ENSP00000366158.2
KCNC3	ENST00000474951.1	c.118+219C>A		intron_variant	Intron 2 of 3	2		ENSP00000432438.1

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 751 AN: 136196 Hom.: 9 Cov.: 18

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00211

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: 0.0000476

Gnomad OTH AF: 0.00480

GnomAD2 exomes AF: 0.00229 AC: 129 AN: 56230 AF XY: 0.00225

Gnomad AFR exome AF: 0.0212

Gnomad AMR exome AF: 0.00140

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: 0.000510

GnomAD4 exome AF: 0.000839 AC: 295 AN: 351410 Hom.: 2 Cov.: 4 AF XY: 0.000694 AC XY: 129 AN XY: 185892

African (AFR) AF: 0.0233 AC: 239 AN: 10244

American (AMR) AF: 0.00143 AC: 23 AN: 16066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10126

East Asian (EAS) AF: 0.00 AC: 0 AN: 21224

South Asian (SAS) AF: 0.0000458 AC: 2 AN: 43634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21736

Middle Eastern (MID) AF: 0.000449 AC: 1 AN: 2226

European-Non Finnish (NFE) AF: 0.0000145 AC: 3 AN: 206260

Other (OTH) AF: 0.00136 AC: 27 AN: 19894

GnomAD4 genome AF: 0.00552 AC: 752 AN: 136282 Hom.: 9 Cov.: 18 AF XY: 0.00539 AC XY: 354 AN XY: 65702

African (AFR) AF: 0.0194 AC: 711 AN: 36556

American (AMR) AF: 0.00210 AC: 29 AN: 13798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3290

East Asian (EAS) AF: 0.00 AC: 0 AN: 4084

South Asian (SAS) AF: 0.00 AC: 0 AN: 3792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.0000476 AC: 3 AN: 63014

Other (OTH) AF: 0.00475 AC: 9 AN: 1894

Alfa AF: 0.00476 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 13, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs78285067; hg19: chr19-50823631;