chr8-139639536-G-T

Variant names:

• chr8-139639536-G-T
• rs1469039
• NM_001282534.2:c.284-20437C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282534.2(KCNK9):​c.284-20437C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 34)
• Consequence: KCNK9 NM_001282534.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282534.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK9	NM_001282534.2	MANE Select	c.284-20437C>A		intron	N/A	NP_001269463.1
	KCNK9	NR_104210.2		n.415-20437C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK9	ENST00000520439.3	TSL:1 MANE Select	c.284-20437C>A		intron	N/A	ENSP00000430676.1
	KCNK9	ENST00000303015.2	TSL:1	c.284-20437C>A		intron	N/A	ENSP00000302166.1
	KCNK9	ENST00000648164.1		c.284-20437C>A		intron	N/A	ENSP00000498198.1

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.55
DANN	Benign	0.63
PhyloP100		-1.9

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: rs1469039; hg19: chr8-140651779;