rs8051542

Variant names:

• chr16-52500255-T-C
• rs8051542
• NM_001080430.4:c.88-31681A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-52500255-T-C
• chr16-52500255-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080430.4(TOX3):​c.88-31681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,040 control chromosomes in the GnomAD database, including 28,673 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 0.61 (28673 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 57 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 = 0.796 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.88-31681A>G		intron	N/A	NP_001073899.2	O15405-1
	TOX3	NM_001146188.2		c.75+19151A>G		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.88-31681A>G		intron	N/A	ENSP00000219746.9	O15405-1
	TOX3	ENST00000912163.1		c.88-31681A>G		intron	N/A	ENSP00000582222.1
	TOX3	ENST00000873102.1		c.88-31681A>G		intron	N/A	ENSP00000543161.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92442 AN: 151924 Hom.: 28642 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.608 AC: 92509 AN: 152040 Hom.: 28673 Cov.: 32 AF XY: 0.610 AC XY: 45379 AN XY: 74334

African (AFR) AF: 0.688 AC: 28519 AN: 41432

American (AMR) AF: 0.576 AC: 8798 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1967 AN: 3470

East Asian (EAS) AF: 0.817 AC: 4223 AN: 5170

South Asian (SAS) AF: 0.701 AC: 3378 AN: 4822

European-Finnish (FIN) AF: 0.519 AC: 5495 AN: 10578

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38230 AN: 67968

Other (OTH) AF: 0.604 AC: 1274 AN: 2110

Alfa AF: 0.577 Hom.: 51002

Bravo AF: 0.614

Asia WGS AF: 0.730 AC: 2539 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	0.55
DANN	Benign	0.35
PhyloP100		-0.57
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: rs8051542; hg19: chr16-52534167;