rs8051542

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.88-31681A>G		intron_variant		ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.75+19151A>G		intron_variant			NP_001139660.1
TOX3	XM_005255892.4	c.88-31681A>G		intron_variant			XP_005255949.1
TOX3	XM_047433909.1	c.75+19151A>G		intron_variant			XP_047289865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.88-31681A>G		intron_variant		2	NM_001080430.4	ENSP00000219746	A2
TOX3	ENST00000407228.7	c.75+19151A>G		intron_variant		2		ENSP00000385705	P2
TOX3	ENST00000563091.1	c.-21-31681A>G		intron_variant		4		ENSP00000457401
TOX3	ENST00000568436.1	c.88-24615A>G		intron_variant, NMD_transcript_variant		3		ENSP00000463843

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

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.604

Alfa AF: 0.576 Hom.: 36791

Bravo AF: 0.614

Asia WGS AF: 0.730 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.55
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs8051542; hg19: chr16-52534167;