16-52449535-A-C

Variant names:

• chr16-52449535-A-C
• rs3095611
• NM_001080430.4:c.678+742T>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.678+742T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,142 control chromosomes in the GnomAD database, including 41,984 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 0.73 (41984 hom., cov: 33)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 4 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080430.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	NM_001080430.4	MANE Select	c.678+742T>G		intron	N/A	NP_001073899.2
	TOX3	NM_001146188.2		c.663+742T>G		intron	N/A	NP_001139660.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	ENST00000219746.14	TSL:2 MANE Select	c.678+742T>G		intron	N/A	ENSP00000219746.9
	TOX3	ENST00000407228.7	TSL:2	c.663+742T>G		intron	N/A	ENSP00000385705.3

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111678 AN: 152024 Hom.: 41940 Cov.: 33

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.735 AC: 111775 AN: 152142 Hom.: 41984 Cov.: 33 AF XY: 0.731 AC XY: 54368 AN XY: 74388

African (AFR) AF: 0.879 AC: 36502 AN: 41542

American (AMR) AF: 0.703 AC: 10733 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2248 AN: 3468

East Asian (EAS) AF: 0.874 AC: 4522 AN: 5172

South Asian (SAS) AF: 0.753 AC: 3630 AN: 4822

European-Finnish (FIN) AF: 0.564 AC: 5949 AN: 10556

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45758 AN: 67990

Other (OTH) AF: 0.715 AC: 1511 AN: 2112

Alfa AF: 0.697 Hom.: 93591

Bravo AF: 0.754

Asia WGS AF: 0.817 AC: 2842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.2
DANN	Benign	0.68
PhyloP100		-0.15
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: rs3095611; hg19: chr16-52483447;