16-52473712-C-G

Variant names:

• chr16-52473712-C-G
• rs16951204
• NM_001080430.4:c.88-5138G>C

Variant summary

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

The NM_001080430.4(TOX3):​c.88-5138G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,070 control chromosomes in the GnomAD database, including 2,926 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 0.17 (2926 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.88-5138G>C		intron_variant	Intron 1 of 6	ENST00000219746.14	NP_001073899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.88-5138G>C		intron_variant	Intron 1 of 6	2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.76-5138G>C		intron_variant	Intron 2 of 7	2		ENSP00000385705.3
TOX3	ENST00000563091.1	c.-21-5138G>C		intron_variant	Intron 1 of 3	4		ENSP00000457401.1
TOX3	ENST00000568436.1	n.*14+1819G>C		intron_variant	Intron 2 of 3	3		ENSP00000463843.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25349 AN: 151952 Hom.: 2926 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.0638

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.167 AC: 25364 AN: 152070 Hom.: 2926 Cov.: 32 AF XY: 0.173 AC XY: 12875 AN XY: 74336

African (AFR) AF: 0.149 AC: 6191 AN: 41496

American (AMR) AF: 0.231 AC: 3529 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0638 AC: 221 AN: 3466

East Asian (EAS) AF: 0.621 AC: 3198 AN: 5148

South Asian (SAS) AF: 0.333 AC: 1607 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1426 AN: 10564

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8678 AN: 67974

Other (OTH) AF: 0.167 AC: 352 AN: 2112

Alfa AF: 0.0517 Hom.: 56

Bravo AF: 0.175

Asia WGS AF: 0.475 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.31
PhyloP100		-0.055
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: rs16951204; hg19: chr16-52507624;