Variant 16-52439419-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001080430.4(TOX3):c.1537C>T(p.Arg513Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 1,546,754 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R513H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 30 hom. )

Consequence

TOX3
NM_001080430.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004915148).

BP6

Variant 16-52439419-G-A is Benign according to our data. Variant chr16-52439419-G-A is described in ClinVar as [Benign]. Clinvar id is 791598.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 666 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX3	NM_001080430.4 linkuse as main transcript	c.1537C>T	p.Arg513Cys	missense_variant	7/7	ENST00000219746.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX3	ENST00000219746.14 linkuse as main transcript	c.1537C>T	p.Arg513Cys	missense_variant	7/7	2	NM_001080430.4	A2	O15405-1
TOX3	ENST00000407228.7 linkuse as main transcript	c.1522C>T	p.Arg508Cys	missense_variant	8/8	2		P2	O15405-2
TOX3	ENST00000566696.1 linkuse as main transcript	n.2001C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

666

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00740

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00436

AC:

758

AN:

173714

Hom.:

AF XY:

0.00446

AC XY:

415

AN XY:

92994

show subpopulations

Gnomad AFR exome

AF:

0.000878

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00206

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.00184

Gnomad NFE exome

AF:

0.00776

Gnomad OTH exome

AF:

0.00528

GnomAD4 exome

AF:

0.00598

AC:

8342

AN:

1394678

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

4034

AN XY:

690976

show subpopulations

Gnomad4 AFR exome

AF:

0.000981

Gnomad4 AMR exome

AF:

0.00319

Gnomad4 ASJ exome

AF:

0.00309

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.00166

Gnomad4 FIN exome

AF:

0.00168

Gnomad4 NFE exome

AF:

0.00714

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.00439

AC:

667

AN:

152076

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

294

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00478

Gnomad4 ASJ

AF:

0.00318

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00740

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00630

Hom.:

Bravo

AF:

0.00424

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.000487

AC:

ESP6500EA

AF:

0.00655

AC:

ExAC

AF:

0.00323

AC:

364

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

Cadd

Pathogenic

Dann

Uncertain

0.99

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.74

.;P

Vest4

0.23

MVP

0.043

MPC

0.29

ClinPred

0.046

GERP RS

5.0

Varity_R

0.17

gMVP

0.083

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