Variant 19-50320374-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_004977.3(KCNC3):c.2171-25C>A variant causes a intron 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 9 hom., cov: 18)

Exomes 𝑓: 0.00084 ( 2 hom. )

Consequence

KCNC3
NM_004977.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.15

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 19-50320374-G-T is Benign according to our data. Variant chr19-50320374-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1344938.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00552 (752/136282) while in subpopulation AFR AF= 0.0194 (711/36556). AF 95% confidence interval is 0.0183. There are 9 homozygotes in gnomad4. There are 354 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.

BS2

High AC in GnomAd4 at 752 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
KCNC3	NM_004977.3 linkuse as main transcript	c.2171-25C>A	intron_variant	ENST00000477616.2	NP_004968.2	Q14003
KCNC3	NM_001372305.1 linkuse as main transcript	c.1943-25C>A	intron_variant		NP_001359234.1
KCNC3	NR_110912.2 linkuse as main transcript	n.260+219C>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
KCNC3	ENST00000477616.2 linkuse as main transcript	c.2171-25C>A	intron_variant	1	NM_004977.3	ENSP00000434241.1	Q14003
KCNC3	ENST00000670667.1 linkuse as main transcript	c.2170+219C>A	intron_variant			ENSP00000499301.1	A0A590UJ62
KCNC3	ENST00000376959.6 linkuse as main transcript	c.2170+219C>A	intron_variant	5		ENSP00000366158.2	E7ETH1
KCNC3	ENST00000474951.1 linkuse as main transcript	c.118+219C>A	intron_variant	2		ENSP00000432438.1	E9PQY4

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

751

AN:

136196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00211

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:

0.0000476

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00229

AC:

129

AN:

56230

Hom.:

AF XY:

0.00225

AC XY:

AN XY:

28394

show subpopulations

Gnomad AFR exome

AF:

0.0212

Gnomad AMR exome

AF:

0.00140

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:

0.000510

GnomAD4 exome

AF:

0.000839

AC:

295

AN:

351410

Hom.:

Cov.:

AF XY:

0.000694

AC XY:

129

AN XY:

185892

show subpopulations

Gnomad4 AFR exome

AF:

0.0233

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000458

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000145

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00552

AC:

752

AN:

136282

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

354

AN XY:

65702

show subpopulations

Gnomad4 AFR

AF:

0.0194

Gnomad4 AMR

AF:

0.00210

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000476

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00476

Hom.:

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

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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