Variant 19-50320323-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_004977.3(KCNC3):c.2197C>A(p.Gln733Lys) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 17)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

KCNC3
NM_004977.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.76

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.116850734).

BP6

Variant 19-50320323-G-T is Benign according to our data. Variant chr19-50320323-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3287524.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCNC3	NM_004977.3 linkuse as main transcript	c.2197C>A	p.Gln733Lys	missense_variant	4/5	ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1 linkuse as main transcript	c.1969C>A	p.Gln657Lys	missense_variant	4/5		NP_001359234.1
KCNC3	NR_110912.2 linkuse as main transcript	n.260+270C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KCNC3	ENST00000477616.2 linkuse as main transcript	c.2197C>A	p.Gln733Lys	missense_variant	4/5	1	NM_004977.3	ENSP00000434241
KCNC3	ENST00000376959.6 linkuse as main transcript	c.2170+270C>A		intron_variant		5		ENSP00000366158	A2
KCNC3	ENST00000474951.1 linkuse as main transcript	c.118+270C>A		intron_variant		2		ENSP00000432438
KCNC3	ENST00000670667.1 linkuse as main transcript	c.2170+270C>A		intron_variant				ENSP00000499301	P3

Frequencies

GnomAD3 genomes

AF:

0.000238

AC:

AN:

130110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000200

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:

0.00345

Gnomad NFE

AF:

0.000362

Gnomad OTH

AF:

0.000559

GnomAD3 exomes

AF:

0.0000553

AC:

AN:

54204

Hom.:

AF XY:

0.0000363

AC XY:

AN XY:

27574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000978

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

AN:

346114

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

AN XY:

177572

show subpopulations

Gnomad4 AFR exome

AF:

0.000207

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000226

Gnomad4 OTH exome

AF:

0.000231

GnomAD4 genome

AF:

0.000238

AC:

AN:

130222

Hom.:

Cov.:

AF XY:

0.000272

AC XY:

AN XY:

62412

show subpopulations

Gnomad4 AFR

AF:

0.000200

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000363

Gnomad4 OTH

AF:

0.000554

Alfa

AF:

0.000279

Hom.:

ExAC

AF:

0.0000159

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.085

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.34

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.21

REVEL

Uncertain

0.34

Sift

Benign

0.29

Sift4G

Benign

0.45

Polyphen

0.0010

Vest4

0.13

MVP

0.72

ClinPred

0.057

GERP RS

2.3

Varity_R

0.063

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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