Variant 16-52439418-C-T 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.1538G>A(p.Arg513His) variant causes a missense change. The variant allele was found at a frequency of 0.0000469 in 1,555,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

TOX3
NM_001080430.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.44

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=0.024678737).

BP6

Variant 16-52439418-C-T is Benign according to our data. Variant chr16-52439418-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3181359.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4 link	c.1538G>A	p.Arg513His	missense_variant	7/7	ENST00000219746.14	NP_001073899.2	O15405-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TOX3	ENST00000219746.14 link	c.1538G>A	p.Arg513His	missense_variant	7/7	2	NM_001080430.4	ENSP00000219746.9	O15405-1
TOX3	ENST00000407228.7 link	c.1523G>A	p.Arg508His	missense_variant	8/8	2		ENSP00000385705.3	O15405-2
TOX3	ENST00000566696.1 link	n.2002G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

182588

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

97934

show subpopulations

Gnomad AFR exome

AF:

0.000203

Gnomad AMR exome

AF:

0.0000385

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000389

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000262

Gnomad OTH exome

AF:

0.000204

GnomAD4 exome

AF:

0.0000456

AC:

AN:

1403360

Hom.:

Cov.:

AF XY:

0.0000474

AC XY:

AN XY:

695652

show subpopulations

Gnomad4 AFR exome

AF:

0.000156

Gnomad4 AMR exome

AF:

0.0000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000532

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000493

Gnomad4 OTH exome

AF:

0.0000343

GnomAD4 genome

AF:

0.0000593

AC:

AN:

151798

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000347

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

.;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.026

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.0

.;B

Vest4

0.14

MutPred

0.31

.;Loss of MoRF binding (P = 0.0141);

MVP

0.043

MPC

0.27

ClinPred

0.11

GERP RS

2.8

Varity_R

0.11

gMVP

0.076

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