17-70132447-G-A

Variant names:

• chr17-70132447-G-A
• rs2074091217
• NM_170741.4:c.360G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_170741.4(KCNJ16):​c.360G>A​(p.Gly120Gly) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNJ16 NM_170741.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.08
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-70132447-G-A is Benign according to our data. Variant chr17-70132447-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3233754.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.08 with no splicing effect.

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.360G>A	p.Gly120Gly	synonymous	Exon 4 of 4	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.360G>A	p.Gly120Gly	synonymous	Exon 6 of 6	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.360G>A	p.Gly120Gly	synonymous	Exon 6 of 6	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.360G>A	p.Gly120Gly	synonymous	Exon 4 of 4	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.360G>A	p.Gly120Gly	synonymous	Exon 5 of 5	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.360G>A	p.Gly120Gly	synonymous	Exon 4 of 4	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.022
DANN	Benign	0.55
PhyloP100		-3.1

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: rs2074091217; hg19: chr17-68128588;