16-52530039-G-T

Variant names:

• chr16-52530039-G-T
• rs1362548
• NM_001080430.4:c.87+16598C>A

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+16598C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 152,092 control chromosomes in the GnomAD database, including 15 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 0.0044 (15 hom., cov: 33)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.87+16598C>A		intron_variant	Intron 1 of 6	ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.-99-10460C>A		intron_variant	Intron 1 of 7		NP_001139660.1
TOX3	XM_005255892.4	c.87+16598C>A		intron_variant	Intron 1 of 6		XP_005255949.1
TOX3	XM_047433909.1	c.-99-10460C>A		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+16598C>A		intron_variant	Intron 1 of 6	2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.-99-10460C>A		intron_variant	Intron 1 of 7	2		ENSP00000385705.3
TOX3	ENST00000563091.1	c.-22+17329C>A		intron_variant	Intron 1 of 3	4		ENSP00000457401.1
TOX3	ENST00000568436.1	n.87+16598C>A		intron_variant	Intron 1 of 3	3		ENSP00000463843.1

Frequencies

GnomAD3 genomes AF: 0.00442 AC: 672 AN: 151974 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.000774

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000473

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.00192

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

GnomAD4 genome AF: 0.00441 AC: 671 AN: 152092 Hom.: 15 Cov.: 33 AF XY: 0.00459 AC XY: 341 AN XY: 74326

African (AFR) AF: 0.000771 AC: 32 AN: 41490

American (AMR) AF: 0.0149 AC: 228 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.0589 AC: 303 AN: 5142

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.000473 AC: 5 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00129 AC: 88 AN: 67998

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.000318 Hom.: 279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.63
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism

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: rs1362548; hg19: chr16-52563951;