16-52547512-C-T

Position:

• chr16-52547512-C-T

Variant summary

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

The NM_001146188.2(TOX3):​c.-100+202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,102 control chromosomes in the GnomAD database, including 10,252 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 0.35 (10213 hom., cov: 29)
  • Exomes 𝑓: 0.30 (39 hom.)
• Consequence: TOX3 NM_001146188.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX3	NM_001146188.2	c.-100+202G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX3	ENST00000407228.7	c.-100+202G>A		intron_variant		2		P2

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53324 AN: 151236 Hom.: 10180 Cov.: 29

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.303 AC: 226 AN: 746 Hom.: 39 Cov.: 0 AF XY: 0.319 AC XY: 159 AN XY: 498

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.563

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.353 AC: 53421 AN: 151356 Hom.: 10213 Cov.: 29 AF XY: 0.355 AC XY: 26280 AN XY: 73934

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.353

Alfa AF: 0.266 Hom.: 2352

Bravo AF: 0.368

Asia WGS AF: 0.431 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.9
DANN	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12930156; hg19: chr16-52581424; COSMIC: COSV54873987; COSMIC: COSV54873987;