rs12443621

Variant names:

• chr16-52514125-A-G
• rs12443621
• NM_001080430.4:c.87+32512T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 67 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080430.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	NM_001080430.4	MANE Select	c.87+32512T>C		intron	N/A	NP_001073899.2	O15405-1
	TOX3	NM_001146188.2		c.75+5281T>C		intron	N/A	NP_001139660.1	O15405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	ENST00000219746.14	TSL:2 MANE Select	c.87+32512T>C		intron	N/A	ENSP00000219746.9	O15405-1
	TOX3	ENST00000912163.1		c.87+32512T>C		intron	N/A	ENSP00000582222.1
	TOX3	ENST00000873102.1		c.87+32512T>C		intron	N/A	ENSP00000543161.1

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

African (AFR) AF: 0.484 AC: 20066 AN: 41480

American (AMR) AF: 0.499 AC: 7615 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1986 AN: 3466

East Asian (EAS) AF: 0.580 AC: 2994 AN: 5166

South Asian (SAS) AF: 0.413 AC: 1990 AN: 4814

European-Finnish (FIN) AF: 0.414 AC: 4366 AN: 10556

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32116 AN: 67960

Other (OTH) AF: 0.491 AC: 1038 AN: 2114

Alfa AF: 0.474 Hom.: 13849

Bravo AF: 0.489

Asia WGS AF: 0.468 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.0
DANN	Benign	0.38
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12443621; hg19: chr16-52548037;