rs12434331

Positions:

• chr14-88293641-T-C

Variant summary

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

The ENST00000319231.10(KCNK10):​c.52+29106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,672 control chromosomes in the GnomAD database, including 3,984 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 0.21 (3984 hom., cov: 30)
• Consequence: KCNK10 ENST00000319231.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136

Genes affected

KCNK10 (HGNC:6273): (potassium two pore domain channel subfamily K member 10) The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations, and is stimulated strongly by arachidonic acid and to a lesser degree by membrane stretching, intracellular acidification, and general anaesthetics. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK10	NM_138317.3	c.52+29106A>G		intron_variant		ENST00000319231.10	NP_612190.1
KCNK10	NM_021161.5	c.38-30090A>G		intron_variant			NP_066984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK10	ENST00000319231.10	c.52+29106A>G		intron_variant		1	NM_138317.3	ENSP00000312811	P1
KCNK10	ENST00000340700.9	c.38-30090A>G		intron_variant		1		ENSP00000343104
KCNK10	ENST00000556282.1	c.1+30006A>G		intron_variant		4		ENSP00000452587

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31770 AN: 151554 Hom.: 3978 Cov.: 30

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.210 AC: 31791 AN: 151672 Hom.: 3984 Cov.: 30 AF XY: 0.217 AC XY: 16042 AN XY: 74068

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.205

Alfa AF: 0.222 Hom.: 5374

Bravo AF: 0.210

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs12434331; hg19: chr14-88759985;