16-52463364-T-G

Variant names:

• chr16-52463364-T-G
• rs11647305
• NM_001080430.4:c.408+570A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080430.4(TOX3):​c.408+570A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,182 control chromosomes in the GnomAD database, including 8,272 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 0.31 (8272 hom., cov: 33)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	NM_001080430.4	MANE Select	c.408+570A>C		intron	N/A	NP_001073899.2
	TOX3	NM_001146188.2		c.393+570A>C		intron	N/A	NP_001139660.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	ENST00000219746.14	TSL:2 MANE Select	c.408+570A>C		intron	N/A	ENSP00000219746.9
	TOX3	ENST00000407228.7	TSL:2	c.393+570A>C		intron	N/A	ENSP00000385705.3
	TOX3	ENST00000563091.1	TSL:4	c.300+570A>C		intron	N/A	ENSP00000457401.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46525 AN: 152064 Hom.: 8273 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.306 AC: 46532 AN: 152182 Hom.: 8272 Cov.: 33 AF XY: 0.301 AC XY: 22405 AN XY: 74406

African (AFR) AF: 0.140 AC: 5796 AN: 41534

American (AMR) AF: 0.287 AC: 4392 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1671 AN: 3472

East Asian (EAS) AF: 0.156 AC: 808 AN: 5172

South Asian (SAS) AF: 0.338 AC: 1635 AN: 4832

European-Finnish (FIN) AF: 0.285 AC: 3013 AN: 10580

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27832 AN: 67988

Other (OTH) AF: 0.338 AC: 715 AN: 2114

Alfa AF: 0.369 Hom.: 12300

Bravo AF: 0.300

Asia WGS AF: 0.234 AC: 818 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		0.78
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: rs11647305; hg19: chr16-52497276;