rs1420529

Variant names:

• chr16-52524761-T-G
• rs1420529
• NM_001080430.4:c.87+21876A>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+21876A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,932 control chromosomes in the GnomAD database, including 25,345 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 0.56 (25345 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.87+21876A>C		intron_variant	Intron 1 of 6	ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.-99-5182A>C		intron_variant	Intron 1 of 7		NP_001139660.1
TOX3	XM_005255892.4	c.87+21876A>C		intron_variant	Intron 1 of 6		XP_005255949.1
TOX3	XM_047433909.1	c.-99-5182A>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+21876A>C		intron_variant	Intron 1 of 6	2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.-99-5182A>C		intron_variant	Intron 1 of 7	2		ENSP00000385705.3
TOX3	ENST00000563091.1	c.-22+22607A>C		intron_variant	Intron 1 of 3	4		ENSP00000457401.1
TOX3	ENST00000568436.1	n.87+21876A>C		intron_variant	Intron 1 of 3	3		ENSP00000463843.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85604 AN: 151814 Hom.: 25293 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.564 AC: 85718 AN: 151932 Hom.: 25345 Cov.: 32 AF XY: 0.559 AC XY: 41504 AN XY: 74240

African (AFR) AF: 0.735 AC: 30468 AN: 41436

American (AMR) AF: 0.545 AC: 8320 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2079 AN: 3464

East Asian (EAS) AF: 0.728 AC: 3749 AN: 5148

South Asian (SAS) AF: 0.464 AC: 2235 AN: 4822

European-Finnish (FIN) AF: 0.437 AC: 4605 AN: 10534

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

European-Non Finnish (NFE) AF: 0.477 AC: 32426 AN: 67952

Other (OTH) AF: 0.560 AC: 1181 AN: 2108

Alfa AF: 0.507 Hom.: 9903

Bravo AF: 0.583

Asia WGS AF: 0.569 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		-0.23
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: rs1420529; hg19: chr16-52558673;