Variant chr19-50314910-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2

The NM_004977.3(KCNC3):c.*1205C>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00139 in 310,674 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

KCNC3
NM_004977.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.91

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.16).

BP6

Variant 19-50314910-G-T is Benign according to our data. Variant chr19-50314910-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2498794.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00274 (417/152214) while in subpopulation AFR AF= 0.00919 (382/41546). AF 95% confidence interval is 0.00843. There are 0 homozygotes in gnomad4. There are 208 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 417 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
KCNC3	NM_004977.3 linkuse as main transcript	c.*1205C>A	3_prime_UTR_variant	5/5	ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1 linkuse as main transcript	c.*1205C>A	3_prime_UTR_variant	5/5		NP_001359234.1
KCNC3	NR_110912.2 linkuse as main transcript	n.400C>A	non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KCNC3	ENST00000477616.2 linkuse as main transcript	c.*1205C>A		3_prime_UTR_variant	5/5	1	NM_004977.3	ENSP00000434241
KCNC3	ENST00000670667.1 linkuse as main transcript	c.2251C>A	p.Pro751Thr	missense_variant	4/4			ENSP00000499301	P3
KCNC3	ENST00000376959.6 linkuse as main transcript	c.*123C>A		3_prime_UTR_variant	5/5	5		ENSP00000366158	A2
KCNC3	ENST00000474951.1 linkuse as main transcript	c.*123C>A		3_prime_UTR_variant	4/4	2		ENSP00000432438

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00922

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

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:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000347

AC:

AN:

14414

Hom.:

AF XY:

0.000505

AC XY:

AN XY:

7920

show subpopulations

Gnomad AFR exome

AF:

0.00501

Gnomad AMR exome

AF:

0.000255

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000884

AC:

AN:

158460

Hom.:

Cov.:

AF XY:

0.0000888

AC XY:

AN XY:

90054

show subpopulations

Gnomad4 AFR exome

AF:

0.00350

Gnomad4 AMR exome

AF:

0.00110

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:

0.000404

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152214

Hom.:

Cov.:

AF XY:

0.00280

AC XY:

208

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00919

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00284

Bravo

AF:

0.00318

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

KCNC3: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

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