16-52501898-T-C

Variant names:

• chr16-52501898-T-C
• rs4784220
• NM_001080430.4:c.88-33324A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080430.4(TOX3):​c.88-33324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,994 control chromosomes in the GnomAD database, including 8,222 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 0.32 (8222 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 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.88-33324A>G		intron	N/A	NP_001073899.2
	TOX3	NM_001146188.2		c.75+17508A>G		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.88-33324A>G		intron	N/A	ENSP00000219746.9
	TOX3	ENST00000407228.7	TSL:2	c.75+17508A>G		intron	N/A	ENSP00000385705.3
	TOX3	ENST00000563091.1	TSL:4	c.-21-33324A>G		intron	N/A	ENSP00000457401.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48195 AN: 151878 Hom.: 8210 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.317 AC: 48216 AN: 151994 Hom.: 8222 Cov.: 32 AF XY: 0.319 AC XY: 23716 AN XY: 74288

African (AFR) AF: 0.209 AC: 8674 AN: 41466

American (AMR) AF: 0.315 AC: 4811 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1697 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1249 AN: 5138

South Asian (SAS) AF: 0.216 AC: 1036 AN: 4802

European-Finnish (FIN) AF: 0.434 AC: 4582 AN: 10564

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24965 AN: 67960

Other (OTH) AF: 0.343 AC: 723 AN: 2108

Alfa AF: 0.349 Hom.: 18445

Bravo AF: 0.307

Asia WGS AF: 0.237 AC: 826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.79
DANN	Benign	0.68
PhyloP100		-0.76
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: rs4784220; hg19: chr16-52535810; COSMIC: COSV54873405;