rs11102146

Positions:

• chr1-110663414-T-C

Variant summary

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

The ENST00000685980.2(KCNA3):​c.*1729-3828A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,158 control chromosomes in the GnomAD database, including 1,343 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 0.13 (1343 hom., cov: 32)
• Consequence: KCNA3 ENST00000685980.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA3	NR_109845.2	n.341-3828A>G		intron_variant, non_coding_transcript_variant
KCNA3	NR_109846.1	n.420-3828A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNA3	ENST00000685980.2	c.*1729-3828A>G		intron_variant, NMD_transcript_variant				ENSP00000513296
KCNA3	ENST00000697409.1	c.*1726-3828A>G		intron_variant, NMD_transcript_variant				ENSP00000513297
KCNA3	ENST00000697410.1	c.*1789-3828A>G		intron_variant, NMD_transcript_variant				ENSP00000513298
KCNA3	ENST00000697411.1	c.*64-3828A>G		intron_variant, NMD_transcript_variant				ENSP00000513299

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19150 AN: 152040 Hom.: 1343 Cov.: 32

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.0822

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.126 AC: 19151 AN: 152158 Hom.: 1343 Cov.: 32 AF XY: 0.121 AC XY: 8979 AN XY: 74396

Gnomad4 AFR AF: 0.0997

Gnomad4 AMR AF: 0.0820

Gnomad4 ASJ AF: 0.0978

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0967

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.111

Alfa AF: 0.140 Hom.: 1501

Bravo AF: 0.121

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11102146; hg19: chr1-111206036;