12-5043889-G-GAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002234.4(KCNA5):c.-259_-258insAA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 506,316 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (11 hom.)
• Consequence: KCNA5 NM_002234.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.868

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-5043889-G-GAA is Benign according to our data. Variant chr12-5043889-G-GAA is described in ClinVar as [Likely_benign]. Clinvar id is 1194327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 553 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA5	NM_002234.4	c.-259_-258insAA		5_prime_UTR_variant	1/1	ENST00000252321.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA5	ENST00000252321.5	c.-259_-258insAA		5_prime_UTR_variant	1/1		NM_002234.4	P1

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 553 AN: 152112 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00507

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00448 AC: 1587 AN: 354086 Hom.: 11 AF XY: 0.00424 AC XY: 785 AN XY: 185356

Gnomad4 AFR exome AF: 0.00101

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.0000901

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000130

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.00489

Gnomad4 OTH exome AF: 0.00403

GnomAD4 genome AF: 0.00363 AC: 553 AN: 152230 Hom.: 1 Cov.: 33 AF XY: 0.00408 AC XY: 304 AN XY: 74442

Gnomad4 AFR AF: 0.000939

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.00507

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00447 Hom.: 0

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1315480835; hg19: chr12-5153055;