chr19-50320375-A-G

Position:

• chr19-50320375-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000477616.2(KCNC3):​c.2171-26T>C 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (69 hom., cov: 12)
  • Exomes 𝑓: 0.019 (60 hom.)
• Consequence: KCNC3 ENST00000477616.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.908

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 19-50320375-A-G is Benign according to our data. Variant chr19-50320375-A-G is described in ClinVar as [Benign]. Clinvar id is 1257797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.2171-26T>C		intron_variant		ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1	c.1943-26T>C		intron_variant			NP_001359234.1
KCNC3	NR_110912.2	n.260+218T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNC3	ENST00000477616.2	c.2171-26T>C		intron_variant		1	NM_004977.3	ENSP00000434241
KCNC3	ENST00000376959.6	c.2170+218T>C		intron_variant		5		ENSP00000366158	A2
KCNC3	ENST00000474951.1	c.118+218T>C		intron_variant		2		ENSP00000432438
KCNC3	ENST00000670667.1	c.2170+218T>C		intron_variant				ENSP00000499301	P3

Frequencies

GnomAD3 genomes AF: 0.0486 AC: 3001 AN: 61686 Hom.: 69 Cov.: 12

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.00936

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00919

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.0667

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0572

GnomAD3 exomes AF: 0.0157 AC: 860 AN: 54766 Hom.: 21 AF XY: 0.0147 AC XY: 406 AN XY: 27586

Gnomad AFR exome AF: 0.0722

Gnomad AMR exome AF: 0.0182

Gnomad ASJ exome AF: 0.00671

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00233

Gnomad FIN exome AF: 0.00558

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.0120

GnomAD4 exome AF: 0.0190 AC: 5004 AN: 262846 Hom.: 60 Cov.: 4 AF XY: 0.0172 AC XY: 2402 AN XY: 139886

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0225

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.000144

Gnomad4 SAS exome AF: 0.00361

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.0204

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0487 AC: 3006 AN: 61706 Hom.: 69 Cov.: 12 AF XY: 0.0513 AC XY: 1435 AN XY: 27976

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0629

Gnomad4 ASJ AF: 0.00936

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00921

Gnomad4 FIN AF: 0.0158

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0566

Alfa AF: 0.0188 Hom.: 21

Bravo AF: 0.0299

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	13
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

Other links and lift over

dbSNP: rs185032351; hg19: chr19-50823632;