chr12-5044717-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_002234.4(KCNA5):c.570C>T(p.Asn190Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,614,142 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 22 hom. )

Consequence

KCNA5
NM_002234.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: -0.537

Publications

5 publications found

Variant links:

Genes affected

KCNA5 (HGNC:6224): (potassium voltage-gated channel subfamily A member 5) Potassium channels represent the most complex class of voltage-gated ino 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, the function of which could restore the resting membrane potential of beta cells after depolarization and thereby contribute to the regulation of insulin secretion. This gene is intronless, and the gene is clustered with genes KCNA1 and KCNA6 on chromosome 12. Defects in this gene are a cause of familial atrial fibrillation type 7 (ATFB7). [provided by RefSeq, May 2012]

KCNA5 Gene-Disease associations (from GenCC):

atrial fibrillation, familial, 7
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KCNA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 12-5044717-C-T is Benign according to our data. Variant chr12-5044717-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 469595.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BP7

Synonymous conserved (PhyloP=-0.537 with no splicing effect.

BS2

High AC in GnomAd4 at 529 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNA5	NM_002234.4 link	c.570C>T	p.Asn190Asn	synonymous_variant	Exon 1 of 1	ENST00000252321.5	NP_002225.2	P22460-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNA5	ENST00000252321.5 link	c.570C>T	p.Asn190Asn	synonymous_variant	Exon 1 of 1	6	NM_002234.4	ENSP00000252321.3		P22460-1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

529

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00830

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00509

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00360

AC:

905

AN:

251344

AF XY:

0.00367

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00786

Gnomad NFE exome

AF:

0.00540

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00488

AC:

7134

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00467

AC XY:

3394

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.000806

AC:

AN:

33480

American (AMR)

AF:

0.00152

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00302

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000128

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00732

AC:

391

AN:

53402

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00573

AC:

6368

AN:

1112008

Other (OTH)

AF:

0.00306

AC:

185

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

520

1040

1559

2079

2599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

244

488

732

976

1220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00347

AC:

529

AN:

152270

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41570

American (AMR)

AF:

0.00235

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00830

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00509

AC:

346

AN:

68024

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00351

Hom.:

Bravo

AF:

0.00303

EpiCase

AF:

0.00431

EpiControl

AF:

0.00421

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Atrial fibrillation, familial, 7

Uncertain:1Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Feb 24, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Oct 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KCNA5: BP4, BP7 -

not specified

Benign:1

Jul 30, 2023

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

KCNA5-related disorder

Benign:1

Sep 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

4.4

(source)

DANN

Benign

0.83

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over