17-70131194-CAAAAAAAA-CAA

Variant names:

• chr17-70131194-CAAAAAA-C
• rs36047658
• NM_170741.4:c.-94+229_-94+234delAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_170741.4(KCNJ16):​c.-94+229_-94+234delAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 21)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768
• Publications: 0 publications found

Genes affected

KCNJ16 (HGNC:6262): (potassium inwardly rectifying channel subfamily J member 16) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which tends to allow potassium to flow into rather than out of a cell, can form heterodimers with two other inward-rectifier type potassium channels. It may function in fluid and pH balance regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

KCNJ16 Gene-Disease associations (from GenCC):

• hypokalemic alkalosis, familial, with specific renal tubulopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hypokalemic tubulopathy and deafness

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170741.4. 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
	KCNJ16	NM_170741.4	MANE Select	c.-94+229_-94+234delAAAAAA		intron	N/A	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.-221-149_-221-144delAAAAAA		intron	N/A	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.-94+229_-94+234delAAAAAA		intron	N/A	NP_001278551.2	Q9NPI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ16	ENST00000392671.6	TSL:2 MANE Select	c.-94+220_-94+225delAAAAAA		intron	N/A	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.-94+220_-94+225delAAAAAA		intron	N/A	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.-94+220_-94+225delAAAAAA		intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes Cov.: 21

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

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36047658; hg19: chr17-68127335;