16-52546074-A-G

Variant names:

• chr16-52546074-A-G
• rs8045285
• NM_001080430.4:c.87+563T>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+563T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,054 control chromosomes in the GnomAD database, including 10,192 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 (10192 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 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+563T>C		intron	N/A	NP_001073899.2	O15405-1
	TOX3	NM_001146188.2		c.-100+1640T>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+563T>C		intron	N/A	ENSP00000219746.9	O15405-1
	TOX3	ENST00000912163.1		c.87+563T>C		intron	N/A	ENSP00000582222.1
	TOX3	ENST00000873102.1		c.87+563T>C		intron	N/A	ENSP00000543161.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52819 AN: 151938 Hom.: 10160 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.348 AC: 52914 AN: 152054 Hom.: 10192 Cov.: 32 AF XY: 0.349 AC XY: 25942 AN XY: 74356

African (AFR) AF: 0.512 AC: 21226 AN: 41460

American (AMR) AF: 0.365 AC: 5586 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1267 AN: 3464

East Asian (EAS) AF: 0.466 AC: 2398 AN: 5146

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4824

European-Finnish (FIN) AF: 0.291 AC: 3082 AN: 10588

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17217 AN: 67968

Other (OTH) AF: 0.340 AC: 718 AN: 2114

Alfa AF: 0.292 Hom.: 3463

Bravo AF: 0.364

Asia WGS AF: 0.347 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		0.96
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: rs8045285; hg19: chr16-52579986;