chr16-52446064-T-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001080430.4(TOX3):c.836A>T(p.Asn279Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000762 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000077 ( 0 hom. )
Consequence
TOX3
NM_001080430.4 missense
NM_001080430.4 missense
Scores
8
8
1
Clinical Significance
Conservation
PhyloP100: 5.13
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.811
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TOX3 | NM_001080430.4 | c.836A>T | p.Asn279Ile | missense_variant | 5/7 | ENST00000219746.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TOX3 | ENST00000219746.14 | c.836A>T | p.Asn279Ile | missense_variant | 5/7 | 2 | NM_001080430.4 | A2 | |
TOX3 | ENST00000407228.7 | c.821A>T | p.Asn274Ile | missense_variant | 6/8 | 2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152186Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
10
AN:
152186
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249232Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135206
GnomAD3 exomes
AF:
AC:
4
AN:
249232
Hom.:
AF XY:
AC XY:
3
AN XY:
135206
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461652Hom.: 0 Cov.: 31 AF XY: 0.0000688 AC XY: 50AN XY: 727118
GnomAD4 exome
AF:
AC:
113
AN:
1461652
Hom.:
Cov.:
31
AF XY:
AC XY:
50
AN XY:
727118
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74356
GnomAD4 genome
?
AF:
AC:
10
AN:
152186
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
74356
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
3
ExAC
?
AF:
AC:
4
EpiCase
AF:
EpiControl
AF:
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 | Apr 13, 2023 | The c.836A>T (p.N279I) alteration is located in exon 5 (coding exon 5) of the TOX3 gene. This alteration results from a A to T substitution at nucleotide position 836, causing the asparagine (N) at amino acid position 279 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MVP
MPC
0.91
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at