rs1116205

Positions:

• chr16-52442951-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080430.4(TOX3):​c.987+1325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,982 control chromosomes in the GnomAD database, including 6,224 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 0.26 (6224 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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 -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 = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.987+1325C>T		intron_variant		ENST00000219746.14	NP_001073899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.987+1325C>T		intron_variant		2	NM_001080430.4	ENSP00000219746	A2
TOX3	ENST00000407228.7	c.972+1325C>T		intron_variant		2		ENSP00000385705	P2
TOX3	ENST00000566696.1	n.1451+1325C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38995 AN: 151864 Hom.: 6225 Cov.: 32

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.256 AC: 38981 AN: 151982 Hom.: 6224 Cov.: 32 AF XY: 0.252 AC XY: 18726 AN XY: 74264

Gnomad4 AFR AF: 0.0914

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.260

Alfa AF: 0.315 Hom.: 1060

Bravo AF: 0.237

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.74

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: rs1116205; hg19: chr16-52476863; COSMIC: COSV54874476;