NM_002232.5:c.*232T>G

Variant names:

• chr1-110672850-A-C
• rs1058184
• NM_002232.5:c.*232T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002232.5(KCNA3):​c.*232T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 500,590 control chromosomes in the GnomAD database, including 113,828 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 0.67 (34209 hom., cov: 31)
  • Exomes 𝑓: 0.67 (79619 hom.)
• Consequence: KCNA3 NM_002232.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814
• Publications: 9 publications found

Genes affected

KCNA3 (HGNC:6221): (potassium voltage-gated channel subfamily A member 3) Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation. This gene appears to be intronless and it is clustered together with KCNA2 and KCNA10 genes on chromosome 1. [provided by RefSeq, Jul 2008]

ENSG00000300042 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNA3	NM_002232.5	c.*232T>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000369769.4	NP_002223.3
KCNA3	NR_109845.2	n.218+387T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNA3	ENST00000369769.4	c.*232T>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_002232.5	ENSP00000358784.2

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101797 AN: 151820 Hom.: 34189 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.671 AC: 233975 AN: 348648 Hom.: 79619 Cov.: 3 AF XY: 0.669 AC XY: 120949 AN XY: 180656

African (AFR) AF: 0.665 AC: 7151 AN: 10750

American (AMR) AF: 0.648 AC: 8155 AN: 12588

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 8734 AN: 11594

East Asian (EAS) AF: 0.531 AC: 14004 AN: 26392

South Asian (SAS) AF: 0.577 AC: 14428 AN: 25024

European-Finnish (FIN) AF: 0.674 AC: 16167 AN: 23982

Middle Eastern (MID) AF: 0.728 AC: 1207 AN: 1658

European-Non Finnish (NFE) AF: 0.696 AC: 149791 AN: 215336

Other (OTH) AF: 0.672 AC: 14338 AN: 21324

GnomAD4 genome AF: 0.670 AC: 101862 AN: 151942 Hom.: 34209 Cov.: 31 AF XY: 0.664 AC XY: 49275 AN XY: 74228

African (AFR) AF: 0.666 AC: 27574 AN: 41420

American (AMR) AF: 0.643 AC: 9822 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2558 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2857 AN: 5144

South Asian (SAS) AF: 0.567 AC: 2722 AN: 4804

European-Finnish (FIN) AF: 0.663 AC: 7007 AN: 10562

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47156 AN: 67962

Other (OTH) AF: 0.685 AC: 1444 AN: 2108

Alfa AF: 0.688 Hom.: 136726

Bravo AF: 0.669

Asia WGS AF: 0.571 AC: 1987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.9
DANN	Benign	0.54
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1058184; hg19: chr1-111215472; COSMIC: COSV63900835;