Variant rs16951186 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080430.4(TOX3):c.382G>A(p.Val128Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,576,708 control chromosomes in the GnomAD database, including 1,577 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.061 ( 796 hom., cov: 33)

Exomes 𝑓: 0.014 ( 781 hom. )

Consequence

TOX3
NM_001080430.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.695

Variant links:

Genes affected

TOX3 (HGNC:11972): (TOX high mobility group box family member 3) The protein encoded by this gene contains an HMG-box, indicating that it may be involved in bending and unwinding of DNA and alteration of chromatin structure. The C-terminus of the encoded protein is glutamine-rich due to CAG repeats in the coding sequence. A minor allele of this gene has been implicated in an elevated risk of breast cancer. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2009]

TOX3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015140474).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4 linkuse as main transcript	c.382G>A	p.Val128Met	missense_variant	3/7	ENST00000219746.14	NP_001073899.2	O15405-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TOX3	ENST00000219746.14 linkuse as main transcript	c.382G>A	p.Val128Met	missense_variant	3/7	2	NM_001080430.4	ENSP00000219746.9	O15405-1
TOX3	ENST00000407228.7 linkuse as main transcript	c.367G>A	p.Val123Met	missense_variant	4/8	2		ENSP00000385705.3	O15405-2
TOX3	ENST00000563091.1 linkuse as main transcript	c.274G>A	p.Val92Met	missense_variant	3/4	4		ENSP00000457401.1	H3BTZ9

Frequencies

GnomAD3 genomes

AF:

0.0611

AC:

9292

AN:

152092

Hom.:

793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00930

Gnomad OTH

AF:

0.0459

GnomAD3 exomes

AF:

0.0211

AC:

4775

AN:

225930

Hom.:

311

AF XY:

0.0180

AC XY:

2199

AN XY:

122072

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.00446

Gnomad EAS exome

AF:

0.000122

Gnomad SAS exome

AF:

0.0154

Gnomad FIN exome

AF:

0.000675

Gnomad NFE exome

AF:

0.00940

Gnomad OTH exome

AF:

0.0159

GnomAD4 exome

AF:

0.0144

AC:

20475

AN:

1424498

Hom.:

781

Cov.:

AF XY:

0.0139

AC XY:

9789

AN XY:

705070

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.0150

Gnomad4 ASJ exome

AF:

0.00536

Gnomad4 EAS exome

AF:

0.0000525

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.000968

Gnomad4 NFE exome

AF:

0.00952

Gnomad4 OTH exome

AF:

0.0219

GnomAD4 genome

AF:

0.0611

AC:

9307

AN:

152210

Hom.:

796

Cov.:

AF XY:

0.0589

AC XY:

4385

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.0262

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00931

Gnomad4 OTH

AF:

0.0455

Alfa

AF:

0.0350

Hom.:

252

Bravo

AF:

0.0695

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.192

AC:

732

ESP6500EA

AF:

0.00970

AC:

ExAC

AF:

0.0239

AC:

2887

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.017

.;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.64

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.28

T;T;.

Polyphen

0.11

.;B;.

Vest4

0.18

MPC

0.40

ClinPred

0.0064

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over