Variant chr1-153975862-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006694.4(JTB):c.248T>G(p.Ile83Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000878 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 0 hom. )

Consequence

JTB
NM_006694.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55

Variant links:

Genes affected

JTB (HGNC:6201): (jumping translocation breakpoint) Enables protein kinase binding activity. Involved in mitotic cytokinesis and positive regulation of protein kinase activity. Located in cytoplasm and midbody. Colocalizes with centrosome and spindle. [provided by Alliance of Genome Resources, Apr 2022]

JTB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JTB	NM_006694.4 linkuse as main transcript	c.248T>G	p.Ile83Ser	missense_variant	4/5	ENST00000271843.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JTB	ENST00000271843.9 linkuse as main transcript	c.248T>G	p.Ile83Ser	missense_variant	4/5	1	NM_006694.4	P1	O76095-1

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000533

AC:

134

AN:

251438

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.000985

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000922

AC:

1347

AN:

1461744

Hom.:

Cov.:

AF XY:

0.000909

AC XY:

661

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000460

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000808

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000638

Hom.:

Bravo

AF:

0.000382

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000535

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000948

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

May 04, 2022

The c.248T>G (p.I83S) alteration is located in exon 4 (coding exon 4) of the JTB gene. This alteration results from a T to G substitution at nucleotide position 248, causing the isoleucine (I) at amino acid position 83 to be replaced by a serine (S). 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

Pathogenic

0.91

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.;.;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;.;.;T

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.5

M;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-4.9

D;D;D;D

REVEL

Uncertain

0.60

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.95

MVP

0.58

MPC

2.0

ClinPred

0.27

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.97

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