Variant chr17-70132278-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PS1_ModeratePM2PP3_StrongPP5

The NM_170741.4(KCNJ16):c.191C>T(p.Thr64Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KCNJ16
NM_170741.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.83

Variant links:

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 links:

KCNJ16 (HGNC:):

KCNJ16 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PS1

Transcript NM_170741.4 (KCNJ16) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.98

PP5

Variant 17-70132278-C-T is Pathogenic according to our data. Variant chr17-70132278-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1174521.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 linkuse as main transcript	c.191C>T	p.Thr64Ile	missense_variant	4/4	ENST00000392671.6	NP_733937.3	Q9NPI9K7EJR9A8K434

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ16	ENST00000392671.6 linkuse as main transcript	c.191C>T	p.Thr64Ile	missense_variant	4/4	2	NM_170741.4	ENSP00000376439.1		Q9NPI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251476

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hypokalemic tubulopathy and deafness

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 28, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.54

BayesDel_noAF

Pathogenic

0.53

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.90

D;D;D;D;.;D;.;.

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

.;.;D;.;D;.;D;D

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.98

D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

2.9

M;M;M;M;.;M;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-5.5

D;D;.;.;.;D;.;.

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

D;D;.;.;.;D;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;.;D;.;.

Vest4

0.96

MutPred

0.88

Loss of catalytic residue at T64 (P = 0.0214);Loss of catalytic residue at T64 (P = 0.0214);Loss of catalytic residue at T64 (P = 0.0214);Loss of catalytic residue at T64 (P = 0.0214);.;Loss of catalytic residue at T64 (P = 0.0214);.;Loss of catalytic residue at T64 (P = 0.0214);

MVP

0.94

MPC

0.44

ClinPred

0.99

GERP RS

6.2

Varity_R

0.90

gMVP

0.90

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over