rs1362548

chr16-52530039-G-Cchr16-52530039-G-T

Variant summary

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

The NM_001080430.4(TOX3):c.87+16598C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,048 control chromosomes in the GnomAD database, including 8,182 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 0.32 (8182 hom., cov: 33)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX3	NM_001080430.4	c.87+16598C>G		intron_variant		ENST00000219746.14
TOX3	NM_001146188.2	c.-99-10460C>G		intron_variant
TOX3	XM_005255892.4	c.87+16598C>G		intron_variant
TOX3	XM_047433909.1	c.-99-10460C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX3	ENST00000219746.14	c.87+16598C>G		intron_variant		2	NM_001080430.4	A2
TOX3	ENST00000407228.7	c.-99-10460C>G		intron_variant		2		P2
TOX3	ENST00000563091.1	c.-22+17329C>G		intron_variant		4
TOX3	ENST00000568436.1	c.87+16598C>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48775 AN: 151930 Hom.: 8166 Cov.: 33

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.321 AC: 48845 AN: 152048 Hom.: 8182 Cov.: 33 AF XY: 0.323 AC XY: 23982 AN XY: 74312

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.323

Alfa AF: 0.159 Hom.: 279

Bravo AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.3
Dann	Benign	0.52

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: rs1362548; hg19: chr16-52563951;