rs12443621

Positions:

• chr16-52514125-A-G

Variant summary

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

The NM_001080430.4(TOX3):​c.87+32512T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,020 control chromosomes in the GnomAD database, including 17,616 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 0.48 (17616 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.87+32512T>C		intron_variant		ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.75+5281T>C		intron_variant			NP_001139660.1
TOX3	XM_005255892.4	c.87+32512T>C		intron_variant			XP_005255949.1
TOX3	XM_047433909.1	c.75+5281T>C		intron_variant			XP_047289865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.87+32512T>C		intron_variant		2	NM_001080430.4	ENSP00000219746	A2
TOX3	ENST00000407228.7	c.75+5281T>C		intron_variant		2		ENSP00000385705	P2
TOX3	ENST00000563091.1	c.-22+33243T>C		intron_variant		4		ENSP00000457401
TOX3	ENST00000568436.1	c.87+32512T>C		intron_variant, NMD_transcript_variant		3		ENSP00000463843

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72736 AN: 151902 Hom.: 17593 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.479 AC: 72807 AN: 152020 Hom.: 17616 Cov.: 32 AF XY: 0.475 AC XY: 35258 AN XY: 74288

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.491

Alfa AF: 0.473 Hom.: 9441

Bravo AF: 0.489

Asia WGS AF: 0.468 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.0
DANN	Benign	0.38

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: rs12443621; hg19: chr16-52548037;