Variant chr19-50320275-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004977.3(KCNC3):c.2245G>A(p.Ala749Thr) variant causes a missense 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 Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

KCNC3
NM_004977.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.92

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25157288).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNC3	NM_004977.3 linkuse as main transcript	c.2245G>A	p.Ala749Thr	missense_variant	4/5	ENST00000477616.2
KCNC3	NM_001372305.1 linkuse as main transcript	c.2017G>A	p.Ala673Thr	missense_variant	4/5
KCNC3	NR_110912.2 linkuse as main transcript	n.260+318G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KCNC3	ENST00000477616.2 linkuse as main transcript	c.2245G>A	p.Ala749Thr	missense_variant	4/5	1	NM_004977.3
KCNC3	ENST00000376959.6 linkuse as main transcript	c.2170+318G>A		intron_variant		5		A2
KCNC3	ENST00000474951.1 linkuse as main transcript	c.118+318G>A		intron_variant		2
KCNC3	ENST00000670667.1 linkuse as main transcript	c.2170+318G>A		intron_variant				P3

Frequencies

GnomAD3 genomes

AF:

0.0000467

AC:

AN:

128458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000872

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:

0.0000802

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000528

AC:

AN:

56842

Hom.:

AF XY:

0.00

AC XY:

AN XY:

29686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000194

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000556

AC:

AN:

916716

Hom.:

Cov.:

AF XY:

0.0000562

AC XY:

AN XY:

444648

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000268

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000662

Gnomad4 OTH exome

AF:

0.0000510

GnomAD4 genome

AF:

0.0000467

AC:

AN:

128458

Hom.:

Cov.:

AF XY:

0.0000328

AC XY:

AN XY:

60942

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000872

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000802

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2021

- -

Spinocerebellar ataxia type 13

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.088

Eigen

Benign

0.014

Eigen_PC

Benign

0.0061

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.25

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.34

REVEL

Uncertain

0.36

Sift

Benign

0.10

Sift4G

Benign

0.25

Polyphen

0.96

Vest4

0.30

MutPred

0.10

Loss of helix (P = 0.0376);

MVP

0.84

ClinPred

0.14

GERP RS

2.3

Varity_R

0.075

gMVP

0.22

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over