Variant 21-38299271-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_170736.3(KCNJ15):c.10A>T(p.Ile4Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KCNJ15
NM_170736.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Variant links:

Genes affected

KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) 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 has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

KCNJ15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12629318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ15	NM_170736.3 linkuse as main transcript	c.10A>T	p.Ile4Phe	missense_variant	3/3	ENST00000398938.7	NP_733932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000398938.7 linkuse as main transcript	c.10A>T	p.Ile4Phe	missense_variant	3/3	1	NM_170736.3	ENSP00000381911	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249432

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459292

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725614

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.10A>T (p.I4F) alteration is located in exon 3 (coding exon 1) of the KCNJ15 gene. This alteration results from a A to T substitution at nucleotide position 10, causing the isoleucine (I) at amino acid position 4 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

9.8

DANN

Benign

0.80

DEOGEN2

Benign

0.10

T;.;.;.;.;.;.;T;T;.;T;T;T;T;T;T;.;T;T;T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.57

T;.;.;.;.;.;T;.;T;T;.;.;T;.;.;.;T;.;.;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.1

.;.;.;.;.;.;.;L;L;.;.;L;.;.;L;L;.;L;L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.9

D;N;N;N;N;N;N;.;.;N;N;N;N;D;N;N;N;N;N;N;N

REVEL

Benign

0.27

Sift

Benign

0.065

.;T;T;T;T;T;T;.;.;T;T;D;D;.;D;D;D;D;D;T;T

Sift4G

Pathogenic

0.0

D;T;T;T;T;T;T;T;T;T;T;T;D;.;T;T;T;T;T;T;T

Polyphen

0.022

.;.;.;.;.;.;.;B;B;.;.;B;.;.;B;B;.;B;B;.;.

Vest4

0.068, 0.079, 0.059

MutPred

0.26

Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);Loss of stability (P = 0.0766);

MVP

0.69

MPC

0.73

ClinPred

0.039

GERP RS

1.2

Varity_R

0.068

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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