19-50320579-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004977.3(KCNC3):c.2170+14C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,608,446 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (1 hom., cov: 29)
  • Exomes 𝑓: 0.00053 (8 hom.)
• Consequence: KCNC3 NM_004977.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0880

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-50320579-G-T is Benign according to our data. Variant chr19-50320579-G-T is described in ClinVar as [Benign]. Clinvar id is 1570014.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000276 (42/151916) while in subpopulation SAS AF= 0.00811 (39/4810). AF 95% confidence interval is 0.0061. There are 1 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNC3	NM_004977.3	c.2170+14C>A		intron_variant		ENST00000477616.2
KCNC3	NM_001372305.1	c.1942+14C>A		intron_variant
KCNC3	NR_110912.2	n.260+14C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNC3	ENST00000477616.2	c.2170+14C>A		intron_variant		1	NM_004977.3
KCNC3	ENST00000376959.6	c.2170+14C>A		intron_variant		5		A2
KCNC3	ENST00000474951.1	c.118+14C>A		intron_variant		2
KCNC3	ENST00000670667.1	c.2170+14C>A		intron_variant				P3

Frequencies

GnomAD3 genomes AF: 0.000277 AC: 42 AN: 151800 Hom.: 1 Cov.: 29

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: 0.00810

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00106 AC: 255 AN: 241046 Hom.: 2 AF XY: 0.00145 AC XY: 190 AN XY: 130858

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00834

Gnomad FIN exome AF: 0.0000494

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.000338

GnomAD4 exome AF: 0.000535 AC: 779 AN: 1456530 Hom.: 8 Cov.: 32 AF XY: 0.000762 AC XY: 552 AN XY: 724326

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00853

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.00000991

Gnomad4 OTH exome AF: 0.000532

GnomAD4 genome AF: 0.000276 AC: 42 AN: 151916 Hom.: 1 Cov.: 29 AF XY: 0.000391 AC XY: 29 AN XY: 74246

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00811

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 26, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.9
Dann	Benign	0.58

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: rs189018316; hg19: chr19-50823836;