chr19-50319151-T-G

Position:

• chr19-50319151-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004977.3(KCNC3):​c.*23+1072A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,912 control chromosomes in the GnomAD database, including 8,328 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8328 hom., cov: 30)
• Consequence: KCNC3 NM_004977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC3	NM_004977.3	c.*23+1072A>C		intron_variant		ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1	c.*23+1072A>C		intron_variant			NP_001359234.1
KCNC3	NR_110912.2	n.260+1442A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNC3	ENST00000477616.2	c.*23+1072A>C		intron_variant		1	NM_004977.3	ENSP00000434241.1
KCNC3	ENST00000670667.1	c.2170+1442A>C		intron_variant				ENSP00000499301.1
KCNC3	ENST00000376959.6	c.2170+1442A>C		intron_variant		5		ENSP00000366158.2
KCNC3	ENST00000474951.1	c.118+1442A>C		intron_variant		2		ENSP00000432438.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46544 AN: 151794 Hom.: 8319 Cov.: 30

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46575 AN: 151912 Hom.: 8328 Cov.: 30 AF XY: 0.312 AC XY: 23141 AN XY: 74252

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.297

Alfa AF: 0.301 Hom.: 6231

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.48

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: rs683856; hg19: chr19-50822408;