rs888345

Variant names:

• chr8-139634747-G-A
• rs888345
• NM_001282534.2:c.284-15648C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-139634747-G-A
• chr8-139634747-G-C
• chr8-139634747-G-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.284-15648C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 151,954 control chromosomes in the GnomAD database, including 50,024 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 0.81 (50024 hom., cov: 31)
• Consequence: KCNK9 NM_001282534.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK9	NM_001282534.2	c.284-15648C>T		intron_variant	Intron 1 of 1	ENST00000520439.3	NP_001269463.1
KCNK9	NR_104210.2	n.415-15648C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK9	ENST00000520439.3	c.284-15648C>T		intron_variant	Intron 1 of 1	1	NM_001282534.2	ENSP00000430676.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 122943 AN: 151836 Hom.: 49975 Cov.: 31

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.810 AC: 123052 AN: 151954 Hom.: 50024 Cov.: 31 AF XY: 0.804 AC XY: 59673 AN XY: 74242

African (AFR) AF: 0.845 AC: 35050 AN: 41488

American (AMR) AF: 0.882 AC: 13490 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2779 AN: 3466

East Asian (EAS) AF: 0.696 AC: 3570 AN: 5126

South Asian (SAS) AF: 0.727 AC: 3480 AN: 4786

European-Finnish (FIN) AF: 0.692 AC: 7294 AN: 10540

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54608 AN: 67946

Other (OTH) AF: 0.830 AC: 1748 AN: 2106

Alfa AF: 0.813 Hom.: 190739

Bravo AF: 0.828

Asia WGS AF: 0.757 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.063
DANN	Benign	0.56
PhyloP100		-2.3
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: rs888345; hg19: chr8-140646990;