rs1420531

chr16-52524922-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080430.4(TOX3):c.87+21715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,336 control chromosomes in the GnomAD database, including 2,286 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2286 hom., cov: 31)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX3	NM_001080430.4	c.87+21715C>T		intron_variant		ENST00000219746.14
TOX3	NM_001146188.2	c.-99-5343C>T		intron_variant
TOX3	XM_005255892.4	c.87+21715C>T		intron_variant
TOX3	XM_047433909.1	c.-99-5343C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX3	ENST00000219746.14	c.87+21715C>T		intron_variant		2	NM_001080430.4	A2
TOX3	ENST00000407228.7	c.-99-5343C>T		intron_variant		2		P2
TOX3	ENST00000563091.1	c.-22+22446C>T		intron_variant		4
TOX3	ENST00000568436.1	c.87+21715C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24433 AN: 151220 Hom.: 2280 Cov.: 31

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24446 AN: 151336 Hom.: 2286 Cov.: 31 AF XY: 0.156 AC XY: 11545 AN XY: 73890

Gnomad4 AFR AF: 0.0737

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.178

Alfa AF: 0.185 Hom.: 769

Bravo AF: 0.161

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.4
Dann	Benign	0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1420531; hg19: chr16-52558834;