Variant 19-50320277-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_004977.3(KCNC3):c.2243A>T(p.Asn748Ile) 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 0.0000084 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNC3
NM_004977.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.369

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30704093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCNC3	NM_004977.3 linkuse as main transcript	c.2243A>T	p.Asn748Ile	missense_variant	4/5	ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1 linkuse as main transcript	c.2015A>T	p.Asn672Ile	missense_variant	4/5		NP_001359234.1
KCNC3	NR_110912.2 linkuse as main transcript	n.260+316A>T		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.2243A>T	p.Asn748Ile	missense_variant	4/5	1	NM_004977.3	ENSP00000434241
KCNC3	ENST00000376959.6 linkuse as main transcript	c.2170+316A>T		intron_variant		5		ENSP00000366158	A2
KCNC3	ENST00000474951.1 linkuse as main transcript	c.118+316A>T		intron_variant		2		ENSP00000432438
KCNC3	ENST00000670667.1 linkuse as main transcript	c.2170+316A>T		intron_variant				ENSP00000499301	P3

Frequencies

GnomAD3 genomes

AF:

0.00000841

AC:

AN:

118920

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:

0.000159

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

819586

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

395086

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000841

AC:

AN:

118920

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

56114

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:

0.00

Gnomad4 FIN

AF:

0.000159

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Mar 15, 2024

The c.2243A>T (p.N748I) alteration is located in exon 4 (coding exon 4) of the KCNC3 gene. This alteration results from a A to T substitution at nucleotide position 2243, causing the asparagine (N) at amino acid position 748 to be replaced by an isoleucine (I). 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

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.095

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.23

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.50

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Polyphen

0.94

Vest4

0.35

MutPred

0.16

Loss of loop (P = 0.0153);

MVP

0.67

ClinPred

0.58

GERP RS

2.2

Varity_R

0.23

gMVP

0.34

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