chr17-70132482-T-TAGG

Position:

• chr17-70132482-T-TAGG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_170741.4(KCNJ16):​c.397_399dupGGA​(p.Gly133dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNJ16 NM_170741.4 conservative_inframe_insertion
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -2.13

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_170741.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 17-70132482-T-TAGG is Pathogenic according to our data. Variant chr17-70132482-T-TAGG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2633613.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ16	NM_170741.4	c.397_399dupGGA	p.Gly133dup	conservative_inframe_insertion	4/4	ENST00000392671.6	NP_733937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ16	ENST00000392671.6	c.397_399dupGGA	p.Gly133dup	conservative_inframe_insertion	4/4	2	NM_170741.4	ENSP00000376439.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

KCNJ16-related disorder Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 2023

The KCNJ16 c.502_504dupGGA variant is predicted to result in an in-frame duplication (p.Gly168dup). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At PreventionGenetics, we have observed this variant in trans with another likely pathogenic variant in a patient with a phenotype consistent with hypokalemic tubulopathy and deafness. Taken together, we interpret this variant as likely pathogenic. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-68128623;