Variant rs375737637 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.1940C>T(p.Pro647Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000387 in 1,548,434 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 (★). Synonymous variant affecting the same amino acid position (i.e. P647P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

KCNC3
NM_004977.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.42037913).

BS2

High AC in GnomAdExome at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNC3	NM_004977.3 linkuse as main transcript	c.1940C>T	p.Pro647Leu	missense_variant	2/5	ENST00000477616.2
KCNC3	NM_001372305.1 linkuse as main transcript	c.1712C>T	p.Pro571Leu	missense_variant	2/5
KCNC3	NR_110912.2 linkuse as main transcript	n.69-2229C>T		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.1940C>T	p.Pro647Leu	missense_variant	2/5	1	NM_004977.3
KCNC3	ENST00000670667.1 linkuse as main transcript	c.1940C>T	p.Pro647Leu	missense_variant	2/4			P3
KCNC3	ENST00000376959.6 linkuse as main transcript	c.1940C>T	p.Pro647Leu	missense_variant	2/5	5		A2
KCNC3	ENST00000474951.1 linkuse as main transcript	c.-74-2229C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152136

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:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000546

AC:

AN:

146510

Hom.:

AF XY:

0.0000507

AC XY:

AN XY:

78926

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:

0.000357

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000408

AC:

AN:

1396298

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

688670

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000506

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000121

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

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:

0.000620

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000866

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 05, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.0028

BayesDel_noAF

Uncertain

0.070

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.42

T;T

MetaSVM

Pathogenic

0.86

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-4.1

D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.18

T;T

Polyphen

1.0

D;D

Vest4

0.27

MutPred

0.27

Loss of helix (P = 0.028);Loss of helix (P = 0.028);

MVP

0.87

ClinPred

0.60

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.52

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