14-90062463-C-A

Variant names:

• chr14-90062463-C-A
• rs1346530520
• NM_022054.4:c.258C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_022054.4(KCNK13):​c.258C>A​(p.Ile86Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,592 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KCNK13 NM_022054.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886
• Publications: 0 publications found

Genes affected

KCNK13 (HGNC:6275): (potassium two pore domain channel subfamily K member 13) 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. This gene encodes a potassium channel containing two pore-forming domains. This protein is an open channel that can be stimulated by arachidonic acid and inhibited by the anesthetic halothane. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.886 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022054.4. 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
	KCNK13	NM_022054.4	MANE Select	c.258C>A	p.Ile86Ile	synonymous	Exon 1 of 2	NP_071337.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK13	ENST00000282146.5	TSL:1 MANE Select	c.258C>A	p.Ile86Ile	synonymous	Exon 1 of 2	ENSP00000282146.4	Q9HB14
	KCNK13	ENST00000954166.1		c.258C>A	p.Ile86Ile	synonymous	Exon 1 of 3	ENSP00000624225.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393592 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 687326

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30988

American (AMR) AF: 0.00 AC: 0 AN: 35624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24766

East Asian (EAS) AF: 0.00 AC: 0 AN: 35772

South Asian (SAS) AF: 0.00 AC: 0 AN: 78212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4220

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077980

Other (OTH) AF: 0.00 AC: 0 AN: 57508

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		0.89
PromoterAI		0.035	Neutral

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: rs1346530520; hg19: chr14-90528807;