Variant rs1001882554 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004977.3(KCNC3):c.1752G>A(p.Pro584Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000469 in 938,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

KCNC3
NM_004977.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.604

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-50323201-C-T is Benign according to our data. Variant chr19-50323201-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 586082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.604 with no splicing effect.

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC3	NM_004977.3 linkuse as main transcript	c.1752G>A	p.Pro584Pro	synonymous_variant	2/5	ENST00000477616.2	NP_004968.2	Q14003
KCNC3	NM_001372305.1 linkuse as main transcript	c.1524G>A	p.Pro508Pro	synonymous_variant	2/5		NP_001359234.1
KCNC3	NR_110912.2 linkuse as main transcript	n.69-2417G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNC3	ENST00000477616.2 linkuse as main transcript	c.1752G>A	p.Pro584Pro	synonymous_variant	2/5	1	NM_004977.3	ENSP00000434241.1	Q14003
KCNC3	ENST00000670667.1 linkuse as main transcript	c.1752G>A	p.Pro584Pro	synonymous_variant	2/4			ENSP00000499301.1	A0A590UJ62
KCNC3	ENST00000376959.6 linkuse as main transcript	c.1752G>A	p.Pro584Pro	synonymous_variant	2/5	5		ENSP00000366158.2	E7ETH1
KCNC3	ENST00000474951.1 linkuse as main transcript	c.-74-2417G>A		intron_variant		2		ENSP00000432438.1	E9PQY4

Frequencies

GnomAD3 genomes

AF:

0.0000601

AC:

AN:

149666

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000265

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000822

AC:

AN:

133782

Hom.:

AF XY:

0.000123

AC XY:

AN XY:

73368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000245

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000444

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000578

Gnomad OTH exome

AF:

0.000244

GnomAD4 exome

AF:

0.0000444

AC:

AN:

788932

Hom.:

Cov.:

AF XY:

0.0000491

AC XY:

AN XY:

407296

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000598

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000330

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000601

AC:

AN:

149666

Hom.:

Cov.:

AF XY:

0.0000684

AC XY:

AN XY:

73082

show subpopulations

Gnomad4 AFR

AF:

0.0000975

Gnomad4 AMR

AF:

0.000265

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000642

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.9

DANN

Benign

0.64

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