rs12600239

Positions:

• chr16-52504988-C-T

Variant summary

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

The NM_001080430.4(TOX3):​c.88-36414G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,980 control chromosomes in the GnomAD database, including 4,995 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 0.25 (4995 hom., cov: 31)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.88-36414G>A		intron_variant		ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.75+14418G>A		intron_variant			NP_001139660.1
TOX3	XM_005255892.4	c.88-36414G>A		intron_variant			XP_005255949.1
TOX3	XM_047433909.1	c.75+14418G>A		intron_variant			XP_047289865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.88-36414G>A		intron_variant		2	NM_001080430.4	ENSP00000219746	A2
TOX3	ENST00000407228.7	c.75+14418G>A		intron_variant		2		ENSP00000385705	P2
TOX3	ENST00000563091.1	c.-21-36414G>A		intron_variant		4		ENSP00000457401
TOX3	ENST00000568436.1	c.88-29348G>A		intron_variant, NMD_transcript_variant		3		ENSP00000463843

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38092 AN: 151862 Hom.: 4986 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.251 AC: 38132 AN: 151980 Hom.: 4995 Cov.: 31 AF XY: 0.254 AC XY: 18825 AN XY: 74254

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.273

Alfa AF: 0.261 Hom.: 625

Bravo AF: 0.252

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.74

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: rs12600239; hg19: chr16-52538900;