NM_001080430.4:c.88-35100C>G

Variant names:

• chr16-52503674-G-C
• rs4784222
• NM_001080430.4:c.88-35100C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080430.4(TOX3):​c.88-35100C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,948 control chromosomes in the GnomAD database, including 13,770 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 0.41 (13770 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.88-35100C>G		intron_variant	Intron 1 of 6	ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.75+15732C>G		intron_variant	Intron 2 of 7		NP_001139660.1
TOX3	XM_005255892.4	c.88-35100C>G		intron_variant	Intron 1 of 6		XP_005255949.1
TOX3	XM_047433909.1	c.75+15732C>G		intron_variant	Intron 2 of 7		XP_047289865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.88-35100C>G		intron_variant	Intron 1 of 6	2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.75+15732C>G		intron_variant	Intron 2 of 7	2		ENSP00000385705.3
TOX3	ENST00000563091.1	c.-21-35100C>G		intron_variant	Intron 1 of 3	4		ENSP00000457401.1
TOX3	ENST00000568436.1	n.88-28034C>G		intron_variant	Intron 1 of 3	3		ENSP00000463843.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62635 AN: 151828 Hom.: 13755 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.413 AC: 62687 AN: 151948 Hom.: 13770 Cov.: 32 AF XY: 0.410 AC XY: 30451 AN XY: 74246

African (AFR) AF: 0.256 AC: 10612 AN: 41450

American (AMR) AF: 0.472 AC: 7211 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1986 AN: 3466

East Asian (EAS) AF: 0.582 AC: 3006 AN: 5168

South Asian (SAS) AF: 0.416 AC: 1997 AN: 4802

European-Finnish (FIN) AF: 0.414 AC: 4360 AN: 10530

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31930 AN: 67946

Other (OTH) AF: 0.451 AC: 951 AN: 2110

Alfa AF: 0.295 Hom.: 754

Bravo AF: 0.413

Asia WGS AF: 0.458 AC: 1594 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.8
DANN	Benign	0.66
PhyloP100		0.44
Mutation Taster		=99/1	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: rs4784222; hg19: chr16-52537586;