chr16-52515734-G-A

Variant names:

• chr16-52515734-G-A
• rs9936081
• NM_001080430.4:c.87+30903C>T

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+30903C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,034 control chromosomes in the GnomAD database, including 7,543 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 (7543 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 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.87+30903C>T		intron	N/A	NP_001073899.2
	TOX3	NM_001146188.2		c.75+3672C>T		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.87+30903C>T		intron	N/A	ENSP00000219746.9
	TOX3	ENST00000407228.7	TSL:2	c.75+3672C>T		intron	N/A	ENSP00000385705.3
	TOX3	ENST00000563091.1	TSL:4	c.-22+31634C>T		intron	N/A	ENSP00000457401.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47113 AN: 151916 Hom.: 7528 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.310 AC: 47168 AN: 152034 Hom.: 7543 Cov.: 32 AF XY: 0.311 AC XY: 23126 AN XY: 74306

African (AFR) AF: 0.385 AC: 15971 AN: 41462

American (AMR) AF: 0.309 AC: 4725 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3464

East Asian (EAS) AF: 0.415 AC: 2143 AN: 5164

South Asian (SAS) AF: 0.215 AC: 1038 AN: 4822

European-Finnish (FIN) AF: 0.291 AC: 3071 AN: 10562

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17906 AN: 67960

Other (OTH) AF: 0.309 AC: 653 AN: 2110

Alfa AF: 0.285 Hom.: 4163

Bravo AF: 0.319

Asia WGS AF: 0.301 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.76
PhyloP100		0.034
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: rs9936081; hg19: chr16-52549646;