rs1801251

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002242.4(KCNJ13):c.524C>T(p.Thr175Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,600,060 control chromosomes in the GnomAD database, including 107,286 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7983 hom., cov: 32)

Exomes 𝑓: 0.36 ( 99303 hom. )

Consequence

KCNJ13
NM_002242.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

KCNJ13 (HGNC:6259): (potassium inwardly rectifying channel subfamily J member 13) This gene encodes a member of the inwardly rectifying potassium channel family of proteins. Members of this family form ion channel pores that allow potassium ions to pass into a cell. The encoded protein belongs to a subfamily of low signal channel conductance proteins that have a low dependence on potassium concentration. Mutations in this gene are associated with snowflake vitreoretinal degeneration. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

KCNJ13 links:

GIGYF2 (HGNC:11960): (GRB10 interacting GYF protein 2) This gene contains CAG trinucleotide repeats and encodes a protein containing several stretches of polyglutamine residues. The encoded protein may be involved in the regulation of tyrosine kinase receptor signaling. This gene is located in a chromosomal region that was genetically linked to Parkinson disease type 11, and mutations in this gene were thought to be causative for this disease. However, more recent studies in different populations have been unable to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

GIGYF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.492368E-5).

BP6

Variant 2-232768750-G-A is Benign according to our data. Variant chr2-232768750-G-A is described in ClinVar as [Benign]. Clinvar id is 335056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232768750-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ13	NM_002242.4 linkuse as main transcript	c.524C>T	p.Thr175Ile	missense_variant	3/3	ENST00000233826.4	NP_002233.2
GIGYF2	NM_001103146.3 linkuse as main transcript	c.532+7314G>A		intron_variant		ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ13	ENST00000233826.4 linkuse as main transcript	c.524C>T	p.Thr175Ile	missense_variant	3/3	1	NM_002242.4	ENSP00000233826	P1	O60928-1
GIGYF2	ENST00000373563.9 linkuse as main transcript	c.532+7314G>A		intron_variant		1	NM_001103146.3	ENSP00000362664	P4	Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48115

AN:

151930

Hom.:

7974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.310

GnomAD3 exomes

AF:

0.349

AC:

86796

AN:

248762

Hom.:

16879

AF XY:

0.367

AC XY:

49373

AN XY:

134420

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.337

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.636

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.361

AC:

523334

AN:

1448012

Hom.:

99303

Cov.:

AF XY:

0.370

AC XY:

265308

AN XY:

717456

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.331

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.627

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.356

Gnomad4 OTH exome

AF:

0.365

GnomAD4 genome

AF:

0.317

AC:

48139

AN:

152048

Hom.:

7983

Cov.:

AF XY:

0.316

AC XY:

23460

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.335

Gnomad4 EAS

AF:

0.332

Gnomad4 SAS

AF:

0.622

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.339

Hom.:

22766

Bravo

AF:

0.309

TwinsUK

AF:

0.361

AC:

1337

ALSPAC

AF:

0.357

AC:

1377

ESP6500AA

AF:

0.265

AC:

1166

ESP6500EA

AF:

0.350

AC:

3013

ExAC

AF:

0.354

AC:

43007

Asia WGS

AF:

0.493

AC:

1712

AN:

3478

EpiCase

AF:

0.347

EpiControl

AF:

0.344

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Leber congenital amaurosis 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.31

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.013

.;T;T

MetaRNN

Benign

0.000075

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.41

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.053

MPC

0.55

ClinPred

0.0062

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.47

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