Genetic Variant KCNC3:c.*1140G>A (chr19-50314975-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004977.3(KCNC3):c.*1140G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNC3
NM_004977.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Publications

0 publications found

Variant links:

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

KCNC3 links:

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ACMG classification

Classification was made for transcript

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 (BayesDel_noAF=-0.2).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3 link	c.*1140G>A	3_prime_UTR_variant	Exon 5 of 5	ENST00000477616.2	NP_004968.2	Q14003
KCNC3	NR_110912.2 link	n.335G>A	non_coding_transcript_exon_variant	Exon 4 of 4
KCNC3	NM_001372305.1 link	c.*1140G>A	3_prime_UTR_variant	Exon 5 of 5		NP_001359234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNC3	ENST00000477616.2 link	c.*1140G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_004977.3	ENSP00000434241.1	Q14003
KCNC3	ENST00000670667.1 link	c.2186G>A	p.Arg729His	missense_variant	Exon 4 of 4			ENSP00000499301.1	A0A590UJ62
KCNC3	ENST00000376959.6 link	c.*58G>A		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000366158.2	E7ETH1
KCNC3	ENST00000474951.1 link	c.*58G>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000432438.1	E9PQY4

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151666

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

111736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

63380

African (AFR)

AF:

0.00

AC:

AN:

748

American (AMR)

AF:

0.00

AC:

AN:

3230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2244

East Asian (EAS)

AF:

0.00

AC:

AN:

966

South Asian (SAS)

AF:

0.00

AC:

AN:

27536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

384

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65176

Other (OTH)

AF:

0.00

AC:

AN:

5156

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41212

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67940

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KCNC3: PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=95/5

polymorphism

(source)

Splicing

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

Publications

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19-50314975-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over