rs1420531

Variant names:

• chr16-52524922-G-A
• rs1420531
• NM_001080430.4:c.87+21715C>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+21715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,336 control chromosomes in the GnomAD database, including 2,286 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 0.16 (2286 hom., cov: 31)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 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+21715C>T		intron	N/A	NP_001073899.2
	TOX3	NM_001146188.2		c.-99-5343C>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+21715C>T		intron	N/A	ENSP00000219746.9
	TOX3	ENST00000407228.7	TSL:2	c.-99-5343C>T		intron	N/A	ENSP00000385705.3
	TOX3	ENST00000563091.1	TSL:4	c.-22+22446C>T		intron	N/A	ENSP00000457401.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24433 AN: 151220 Hom.: 2280 Cov.: 31

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.162 AC: 24446 AN: 151336 Hom.: 2286 Cov.: 31 AF XY: 0.156 AC XY: 11545 AN XY: 73890

African (AFR) AF: 0.0737 AC: 3035 AN: 41202

American (AMR) AF: 0.187 AC: 2850 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3466

East Asian (EAS) AF: 0.156 AC: 802 AN: 5138

South Asian (SAS) AF: 0.198 AC: 947 AN: 4784

European-Finnish (FIN) AF: 0.124 AC: 1283 AN: 10380

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.209 AC: 14197 AN: 67842

Other (OTH) AF: 0.178 AC: 375 AN: 2106

Alfa AF: 0.187 Hom.: 1381

Bravo AF: 0.161

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.25
PhyloP100		-0.30
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: rs1420531; hg19: chr16-52558834;