Genetic Variant KCNC3:c.*1172G>A (chr19-50314943-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4BS1BS2

The NM_004977.3(KCNC3):c.*1172G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 302,466 control chromosomes in the GnomAD database, including 8 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 0.00060 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 7 hom. )

Consequence

KCNC3
NM_004977.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0530

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.13).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000598 (91/152086) while in subpopulation SAS AF= 0.0185 (89/4818). AF 95% confidence interval is 0.0154. There are 1 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 91 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3 link	c.*1172G>A	3_prime_UTR_variant	Exon 5 of 5	ENST00000477616.2	NP_004968.2	Q14003
KCNC3	NM_001372305.1 link	c.*1172G>A	3_prime_UTR_variant	Exon 5 of 5		NP_001359234.1
KCNC3	NR_110912.2 link	n.367G>A	non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNC3	ENST00000477616 link	c.*1172G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_004977.3	ENSP00000434241.1	Q14003
KCNC3	ENST00000670667.1 link	c.2218G>A	p.Val740Met	missense_variant	Exon 4 of 4			ENSP00000499301.1	A0A590UJ62
KCNC3	ENST00000376959 link	c.*90G>A		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000366158.2	E7ETH1
KCNC3	ENST00000474951 link	c.*90G>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000432438.1	E9PQY4

Frequencies

GnomAD3 genomes

AF:

0.000599

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0185

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00157

AC:

AN:

12706

Hom.:

AF XY:

0.00186

AC XY:

AN XY:

6986

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00730

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00251

AC:

377

AN:

150380

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

319

AN XY:

85354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000205

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000570

GnomAD4 genome

AF:

0.000598

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.000928

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0185

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.000132

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over