19-50320232-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004977.3(KCNC3):c.*13del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (4 hom., cov: 15)
  • Exomes 𝑓: 0.0030 (3 hom.)
• Consequence: KCNC3 NM_004977.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.422

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 -10 ACMG points.

• BP6: Variant 19-50320232-AG-A is Benign according to our data. Variant chr19-50320232-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1698028.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0151 (417/27650) while in subpopulation AFR AF= 0.0483 (335/6936). AF 95% confidence interval is 0.044. There are 4 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 15. This position pass quality control queck.
• BS2: High AC in GnomAd at 416 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNC3	NM_004977.3	c.*13del		3_prime_UTR_variant	4/5	ENST00000477616.2
KCNC3	NM_001372305.1	c.*13del		3_prime_UTR_variant	4/5
KCNC3	NR_110912.2	n.260+360del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNC3	ENST00000477616.2	c.*13del		3_prime_UTR_variant	4/5	1	NM_004977.3
KCNC3	ENST00000376959.6	c.2170+360del		intron_variant		5		A2
KCNC3	ENST00000474951.1	c.118+360del		intron_variant		2
KCNC3	ENST00000670667.1	c.2170+360del		intron_variant				P3

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 416 AN: 27644 Hom.: 4 Cov.: 15

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00404

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.0123

GnomAD3 exomes AF: 0.00258 AC: 65 AN: 25174 Hom.: 1 AF XY: 0.00203 AC XY: 27 AN XY: 13312

Gnomad AFR exome AF: 0.0186

Gnomad AMR exome AF: 0.000324

Gnomad ASJ exome AF: 0.0189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000479

Gnomad OTH exome AF: 0.00387

GnomAD4 exome AF: 0.00305 AC: 399 AN: 130994 Hom.: 3 Cov.: 7 AF XY: 0.00294 AC XY: 194 AN XY: 66002

Gnomad4 AFR exome AF: 0.0397

Gnomad4 AMR exome AF: 0.00207

Gnomad4 ASJ exome AF: 0.0447

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000422

Gnomad4 OTH exome AF: 0.00727

GnomAD4 genome AF: 0.0151 AC: 417 AN: 27650 Hom.: 4 Cov.: 15 AF XY: 0.0140 AC XY: 180 AN XY: 12814

Gnomad4 AFR AF: 0.0483

Gnomad4 AMR AF: 0.00404

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000853

Gnomad4 OTH AF: 0.0122

Alfa AF: 0.00430 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 19, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

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: rs759727454; hg19: chr19-50823489;