ENST00000685980.2:n.*1606+850G>T – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000685980.2(KCNA3):n.*1606+850G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,930 control chromosomes in the GnomAD database, including 34,587 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 ( 34587 hom., cov: 32)

Consequence

KCNA3
ENST00000685980.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0790

Publications

4 publications found

Variant links:

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]

KCNA3 links:

ENSG00000300042 (HGNC:):

ENSG00000300042 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000685980.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNA3	NR_109845.2		n.219-2282G>T		intron	N/A
	KCNA3	NR_109846.1		n.300+850G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNA3	ENST00000685980.2	n.*1606+850G>T	intron	N/A	ENSP00000513296.1	P22001-1
KCNA3	ENST00000697409.1	n.*1606+850G>T	intron	N/A	ENSP00000513297.1	P22001-1
KCNA3	ENST00000697410.1	n.*1607-797G>T	intron	N/A	ENSP00000513298.1	P22001-1

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102377

AN:

151812

Hom.:

34561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.680

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.644

Gnomad ASJ

AF:

0.737

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.564

Gnomad FIN

AF:

0.665

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.688

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

GnomAD4 genome

AF:

0.674

AC:

102456

AN:

151930

Hom.:

34587

Cov.:

AF XY:

0.668

AC XY:

49581

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.680

AC:

28156

AN:

41416

American (AMR)

AF:

0.645

AC:

9833

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.737

AC:

2558

AN:

3472

East Asian (EAS)

AF:

0.555

AC:

2869

AN:

5166

South Asian (SAS)

AF:

0.565

AC:

2716

AN:

4808

European-Finnish (FIN)

AF:

0.665

AC:

7014

AN:

10554

Middle Eastern (MID)

AF:

0.697

AC:

205

AN:

294

European-Non Finnish (NFE)

AF:

0.694

AC:

47137

AN:

67940

Other (OTH)

AF:

0.686

AC:

1450

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1761

3522

5284

7045

8806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.691

Hom.:

44344

Bravo

AF:

0.673

Asia WGS

AF:

0.567

AC:

1971

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.0

(source)

DANN

Benign

0.50

PhyloP100

-0.079

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over