Variant chr19-50320314-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004977.3(KCNC3):c.2206C>T(p.Arg736Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000024 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

KCNC3
NM_004977.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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:

KCNC3 (HGNC:):

KCNC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30502015).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC3	NM_004977.3 linkuse as main transcript	c.2206C>T	p.Arg736Cys	missense_variant	4/5	ENST00000477616.2	NP_004968.2	Q14003
KCNC3	NM_001372305.1 linkuse as main transcript	c.1978C>T	p.Arg660Cys	missense_variant	4/5		NP_001359234.1
KCNC3	NR_110912.2 linkuse as main transcript	n.260+279C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNC3	ENST00000477616.2 linkuse as main transcript	c.2206C>T	p.Arg736Cys	missense_variant	4/5	1	NM_004977.3	ENSP00000434241.1	Q14003
KCNC3	ENST00000670667.1 linkuse as main transcript	c.2170+279C>T		intron_variant				ENSP00000499301.1	A0A590UJ62
KCNC3	ENST00000376959.6 linkuse as main transcript	c.2170+279C>T		intron_variant		5		ENSP00000366158.2	E7ETH1
KCNC3	ENST00000474951.1 linkuse as main transcript	c.118+279C>T		intron_variant		2		ENSP00000432438.1	E9PQY4

Frequencies

GnomAD3 genomes

AF:

0.0000237

AC:

AN:

126460

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:

0.000320

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000334

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000280

AC:

AN:

427814

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

214378

show subpopulations

Gnomad4 AFR exome

AF:

0.000174

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000107

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000194

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000237

AC:

AN:

126460

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

60340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000320

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000334

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.2206C>T (p.R736C) alteration is located in exon 4 (coding exon 4) of the KCNC3 gene. This alteration results from a C to T substitution at nucleotide position 2206, causing the arginine (R) at amino acid position 736 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.068

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.21

REVEL

Uncertain

0.35

Sift

Benign

0.12

Sift4G

Uncertain

0.056

Polyphen

0.94

Vest4

0.16

MutPred

0.22

Loss of solvent accessibility (P = 0.0352);

MVP

0.75

ClinPred

0.25

GERP RS

2.3

Varity_R

0.11

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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