Variant 8-142664692-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003724.4(JRK):c.1367C>T(p.Thr456Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000761 in 1,609,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 0 hom. )

Consequence

JRK
NM_003724.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.583

Variant links:

Genes affected

JRK (HGNC:6199): (Jrk helix-turn-helix protein) This gene encodes a conserved protein that is similar to DNA-binding proteins, such as major centromere autoantigen B (CENPB). Inactivation of the related gene in mice resulted in epileptic seizures. Childhood Absence Epilepsy (CAE) has been mapped to the same chromosomal location (8q24.3) as this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

JRK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02662149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JRK	NM_003724.4 linkuse as main transcript	c.1367C>T	p.Thr456Met	missense_variant	2/2	ENST00000612905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JRK	ENST00000612905.2 linkuse as main transcript	c.1367C>T	p.Thr456Met	missense_variant	2/2	2	NM_003724.4	P2	O75564-2
JRK	ENST00000614134.1 linkuse as main transcript	c.1367C>T	p.Thr456Met	missense_variant	2/2	1		P2	O75564-2
JRK	ENST00000571961.7 linkuse as main transcript	c.1367C>T	p.Thr456Met	missense_variant	2/3	1		A2	O75564-1
JRK	ENST00000615982.4 linkuse as main transcript	c.1367C>T	p.Thr456Met	missense_variant	2/4	1		A2	O75564-1

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000426

AC:

100

AN:

234606

Hom.:

AF XY:

0.000428

AC XY:

AN XY:

128576

show subpopulations

Gnomad AFR exome

AF:

0.000514

Gnomad AMR exome

AF:

0.000207

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000391

Gnomad NFE exome

AF:

0.000737

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000786

AC:

1146

AN:

1457322

Hom.:

Cov.:

AF XY:

0.000755

AC XY:

547

AN XY:

724602

show subpopulations

Gnomad4 AFR exome

AF:

0.000479

Gnomad4 AMR exome

AF:

0.000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000230

Gnomad4 NFE exome

AF:

0.000958

Gnomad4 OTH exome

AF:

0.000714

GnomAD4 genome

AF:

0.000519

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000521

Hom.:

Bravo

AF:

0.000650

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00110

AC:

ExAC

AF:

0.000449

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

JRK: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.27

DANN

Benign

0.61

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.43

.;T;.;T

MetaRNN

Benign

0.027

T;T;T;T

PrimateAI

Benign

0.31

Sift4G

Uncertain

0.046

D;D;D;D

Vest4

0.64

MVP

0.42

GERP RS

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.25

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