17-70132482-T-TAGG

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PM4_Supporting PP5_Moderate

The NM_170741.4(KCNJ16):c.397_399dup(p.Gly133dup) variant causes a 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNJ16 NM_170741.4 inframe_insertion
• Clinical Significance: Likely pathogenic criteria provided, single submitter 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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a intramembrane_region Pore-forming (size 6) in uniprot entity KCJ16_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_170741.4
• 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 criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ16	NM_170741.4	c.397_399dup	p.Gly133dup	inframe_insertion	4/4	ENST00000392671.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ16	ENST00000392671.6	c.397_399dup	p.Gly133dup	inframe_insertion	4/4	2	NM_170741.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

KCNJ16-related disorder Pathogenic:1

Likely pathogenic, criteria provided, single submitter

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;