rs1420533

Variant names:

• chr16-52529714-G-A
• rs1420533
• NM_001080430.4:c.87+16923C>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+16923C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,062 control chromosomes in the GnomAD database, including 26,075 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 0.57 (26075 hom., cov: 33)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 11 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 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+16923C>T		intron	N/A	NP_001073899.2
	TOX3	NM_001146188.2		c.-99-10135C>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+16923C>T		intron	N/A	ENSP00000219746.9
	TOX3	ENST00000407228.7	TSL:2	c.-99-10135C>T		intron	N/A	ENSP00000385705.3
	TOX3	ENST00000563091.1	TSL:4	c.-22+17654C>T		intron	N/A	ENSP00000457401.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86778 AN: 151944 Hom.: 26018 Cov.: 33

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.571 AC: 86901 AN: 152062 Hom.: 26075 Cov.: 33 AF XY: 0.567 AC XY: 42136 AN XY: 74300

African (AFR) AF: 0.736 AC: 30523 AN: 41486

American (AMR) AF: 0.589 AC: 8995 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3470

East Asian (EAS) AF: 0.780 AC: 4043 AN: 5182

South Asian (SAS) AF: 0.467 AC: 2249 AN: 4816

European-Finnish (FIN) AF: 0.442 AC: 4657 AN: 10534

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32510 AN: 67988

Other (OTH) AF: 0.572 AC: 1206 AN: 2110

Alfa AF: 0.510 Hom.: 83106

Bravo AF: 0.593

Asia WGS AF: 0.603 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.43
DANN	Benign	0.29
PhyloP100		-0.19
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: rs1420533; hg19: chr16-52563626;