rs1123428

Positions:

• chr16-52543923-T-A
• chr16-52543923-T-C
• chr16-52543923-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080430.4(TOX3):​c.87+2714A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,920 control chromosomes in the GnomAD database, including 20,475 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 0.51 (20475 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX3	NM_001080430.4	c.87+2714A>T		intron_variant		ENST00000219746.14
TOX3	NM_001146188.2	c.-100+3791A>T		intron_variant
TOX3	XM_005255892.4	c.87+2714A>T		intron_variant
TOX3	XM_047433909.1	c.-100+2714A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX3	ENST00000219746.14	c.87+2714A>T		intron_variant		2	NM_001080430.4	A2
TOX3	ENST00000407228.7	c.-100+3791A>T		intron_variant		2		P2
TOX3	ENST00000563091.1	c.-22+3445A>T		intron_variant		4
TOX3	ENST00000568436.1	c.87+2714A>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77944 AN: 151800 Hom.: 20437 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.514 AC: 78045 AN: 151920 Hom.: 20475 Cov.: 32 AF XY: 0.509 AC XY: 37775 AN XY: 74240

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.520

Alfa AF: 0.491 Hom.: 2226

Bravo AF: 0.530

Asia WGS AF: 0.512 AC: 1781 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs1123428; hg19: chr16-52577835;