rs4784222

Positions:

• chr16-52503674-G-A
• chr16-52503674-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001080430.4(TOX3):​c.88-35100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 152,022 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00068 (0 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAd4 at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.88-35100C>T		intron_variant		ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.75+15732C>T		intron_variant			NP_001139660.1
TOX3	XM_005255892.4	c.88-35100C>T		intron_variant			XP_005255949.1
TOX3	XM_047433909.1	c.75+15732C>T		intron_variant			XP_047289865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.88-35100C>T		intron_variant		2	NM_001080430.4	ENSP00000219746	A2
TOX3	ENST00000407228.7	c.75+15732C>T		intron_variant		2		ENSP00000385705	P2
TOX3	ENST00000563091.1	c.-21-35100C>T		intron_variant		4		ENSP00000457401
TOX3	ENST00000568436.1	c.88-28034C>T		intron_variant, NMD_transcript_variant		3		ENSP00000463843

Frequencies

GnomAD3 genomes AF: 0.000678 AC: 103 AN: 151902 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000678 AC: 103 AN: 152022 Hom.: 0 Cov.: 32 AF XY: 0.000592 AC XY: 44 AN XY: 74292

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000949

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000993 Hom.: 754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.2
DANN	Benign	0.49

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: rs4784222; hg19: chr16-52537586;