rs3095611

chr16-52449535-A-Cchr16-52449535-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080430.4(TOX3):c.678+742T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,142 control chromosomes in the GnomAD database, including 41,984 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 0.73 (41984 hom., cov: 33)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX3	NM_001080430.4	c.678+742T>G		intron_variant		ENST00000219746.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX3	ENST00000219746.14	c.678+742T>G		intron_variant		2	NM_001080430.4	A2
TOX3	ENST00000407228.7	c.663+742T>G		intron_variant		2		P2

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111678 AN: 152024 Hom.: 41940 Cov.: 33

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.735 AC: 111775 AN: 152142 Hom.: 41984 Cov.: 33 AF XY: 0.731 AC XY: 54368 AN XY: 74388

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.874

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.715

Alfa AF: 0.680 Hom.: 30887

Bravo AF: 0.754

Asia WGS AF: 0.817 AC: 2842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	4.2
Dann	Benign	0.68

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: rs3095611; hg19: chr16-52483447;