8-139681497-C-A

Variant names:

• chr8-139681497-C-A
• rs983740
• NM_001282534.2:c.283+21213G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282534.2(KCNK9):​c.283+21213G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,150 control chromosomes in the GnomAD database, including 22,669 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 0.54 (22669 hom., cov: 34)
• Consequence: KCNK9 NM_001282534.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.45
• Publications: 3 publications found

Genes affected

KCNK9 (HGNC:6283): (potassium two pore domain channel subfamily K member 9) This gene encodes a protein that contains multiple transmembrane regions and two pore-forming P domains and functions as a pH-dependent potassium channel. Amplification and overexpression of this gene have been observed in several types of human carcinomas. This gene is imprinted in the brain, with preferential expression from the maternal allele. A mutation in this gene was associated with Birk-Barel dysmorphism syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

KCNK9 Gene-Disease associations (from GenCC):

• Birk-Barel syndrome

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK9	NM_001282534.2	c.283+21213G>T		intron_variant	Intron 1 of 1	ENST00000520439.3	NP_001269463.1
KCNK9	NR_104210.2	n.414+21213G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK9	ENST00000520439.3	c.283+21213G>T		intron_variant	Intron 1 of 1	1	NM_001282534.2	ENSP00000430676.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82469 AN: 152032 Hom.: 22661 Cov.: 34

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.542 AC: 82510 AN: 152150 Hom.: 22669 Cov.: 34 AF XY: 0.543 AC XY: 40387 AN XY: 74344

African (AFR) AF: 0.460 AC: 19122 AN: 41532

American (AMR) AF: 0.594 AC: 9077 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1745 AN: 5162

South Asian (SAS) AF: 0.587 AC: 2829 AN: 4822

European-Finnish (FIN) AF: 0.615 AC: 6496 AN: 10562

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39691 AN: 68002

Other (OTH) AF: 0.516 AC: 1089 AN: 2112

Alfa AF: 0.513 Hom.: 3747

Bravo AF: 0.536

Asia WGS AF: 0.497 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.55
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs983740; hg19: chr8-140693740;