GeneBe

rs886049503

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000217.3(KCNA1):​c.-636G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KCNA1
NM_000217.3 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.623

Publications

0 publications found
Variant links:
Genes affected
KCNA1 (HGNC:6218): (potassium voltage-gated channel subfamily A member 1) This gene encodes a voltage-gated delayed potassium channel that is phylogenetically related to the Drosophila Shaker channel. The encoded protein has six putative transmembrane segments (S1-S6), and the loop between S5 and S6 forms the pore and contains the conserved selectivity filter motif (GYGD). The functional channel is a homotetramer. The N-terminus of the channel is associated with beta subunits that can modify the inactivation properties of the channel as well as affect expression levels. The C-terminus of the channel is complexed to a PDZ domain protein that is responsible for channel targeting. Mutations in this gene have been associated with myokymia with periodic ataxia (AEMK). [provided by RefSeq, Jul 2008]
KCNA1 Gene-Disease associations (from GenCC):
  • episodic ataxia type 1
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • episodic kinesigenic dyskinesia 1
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • isolated autosomal dominant hypomagnesemia, Glaudemans type
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • genetic developmental and epileptic encephalopathy
    Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNA1NM_000217.3 linkc.-636G>A 5_prime_UTR_variant Exon 1 of 2 ENST00000382545.5 NP_000208.2 Q09470

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNA1ENST00000382545.5 linkc.-636G>A 5_prime_UTR_variant Exon 1 of 2 4 NM_000217.3 ENSP00000371985.3 Q09470

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
94
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
76
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
2
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
84
Other (OTH)
AC:
0
AN:
0
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
8.5
DANN
Benign
0.92
PhyloP100
0.62
PromoterAI
0.022
Neutral

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

Other links and lift over

dbSNP: rs886049503; hg19: chr12-5019542; API