16-52532542-T-G

Variant names:

• chr16-52532542-T-G
• rs2193094
• NM_001080430.4:c.87+14095A>C

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+14095A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,150 control chromosomes in the GnomAD database, including 31,523 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 0.62 (31523 hom., cov: 33)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 9 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.87+14095A>C		intron_variant	Intron 1 of 6	ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.-99-12963A>C		intron_variant	Intron 1 of 7		NP_001139660.1
TOX3	XM_005255892.4	c.87+14095A>C		intron_variant	Intron 1 of 6		XP_005255949.1
TOX3	XM_047433909.1	c.-99-12963A>C		intron_variant	Intron 1 of 7		XP_047289865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.87+14095A>C		intron_variant	Intron 1 of 6	2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.-99-12963A>C		intron_variant	Intron 1 of 7	2		ENSP00000385705.3
TOX3	ENST00000563091.1	c.-22+14826A>C		intron_variant	Intron 1 of 3	4		ENSP00000457401.1
TOX3	ENST00000568436.1	n.87+14095A>C		intron_variant	Intron 1 of 3	3		ENSP00000463843.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93643 AN: 152032 Hom.: 31454 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.616 AC: 93780 AN: 152150 Hom.: 31523 Cov.: 33 AF XY: 0.611 AC XY: 45457 AN XY: 74368

African (AFR) AF: 0.888 AC: 36901 AN: 41540

American (AMR) AF: 0.609 AC: 9317 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3468

East Asian (EAS) AF: 0.786 AC: 4059 AN: 5164

South Asian (SAS) AF: 0.468 AC: 2257 AN: 4826

European-Finnish (FIN) AF: 0.443 AC: 4679 AN: 10556

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32560 AN: 67986

Other (OTH) AF: 0.606 AC: 1282 AN: 2116

Alfa AF: 0.507 Hom.: 10316

Bravo AF: 0.644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.83
PhyloP100		0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2193094; hg19: chr16-52566454;