Variant chr19-50314777-TCCCCACC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004977.3(KCNC3):c.*1331_*1337delGGTGGGG variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000659 in 151,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNC3
NM_004977.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3 link	c.1331_1337delGGTGGGG	3_prime_UTR_variant	Exon 5 of 5	ENST00000477616.2	NP_004968.2	Q14003
KCNC3	NM_001372305.1 link	c.1331_1337delGGTGGGG	3_prime_UTR_variant	Exon 5 of 5		NP_001359234.1
KCNC3	NR_110912.2 link	n.526_532delGGTGGGG	non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNC3	ENST00000477616 link	c.1331_1337delGGTGGGG	3_prime_UTR_variant	Exon 5 of 5	1	NM_004977.3	ENSP00000434241.1	Q14003
KCNC3	ENST00000670667 link	c.70_76delGGTGGGG	3_prime_UTR_variant	Exon 4 of 4			ENSP00000499301.1	A0A590UJ62
KCNC3	ENST00000376959 link	c.249_255delGGTGGGG	3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000366158.2	E7ETH1
KCNC3	ENST00000474951 link	c.249_255delGGTGGGG	3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000432438.1	E9PQY4

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151794

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

269716

Hom.:

AF XY:

0.00

AC XY:

AN XY:

155018

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Mar 15, 2024

Variant summary: KCNC3 c.*1331_*1337delGGTGGGG is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 2.4e-06 in 421510 control chromosomes (gnomAD v4.0). The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.*1331_*1337delGGTGGGG in individuals affected with Spinocerebellar Ataxia Type 13 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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