chr16-52502973-C-T

Variant names:

• chr16-52502973-C-T
• rs12598982
• NM_001080430.4:c.88-34399G>A

Variant summary

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

The NM_001080430.4(TOX3):​c.88-34399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,994 control chromosomes in the GnomAD database, including 13,479 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 0.40 (13479 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.88-34399G>A		intron_variant	Intron 1 of 6	ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.75+16433G>A		intron_variant	Intron 2 of 7		NP_001139660.1
TOX3	XM_005255892.4	c.88-34399G>A		intron_variant	Intron 1 of 6		XP_005255949.1
TOX3	XM_047433909.1	c.75+16433G>A		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.88-34399G>A		intron_variant	Intron 1 of 6	2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.75+16433G>A		intron_variant	Intron 2 of 7	2		ENSP00000385705.3
TOX3	ENST00000563091.1	c.-21-34399G>A		intron_variant	Intron 1 of 3	4		ENSP00000457401.1
TOX3	ENST00000568436.1	n.88-27333G>A		intron_variant	Intron 1 of 3	3		ENSP00000463843.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61329 AN: 151876 Hom.: 13466 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.404 AC: 61379 AN: 151994 Hom.: 13479 Cov.: 32 AF XY: 0.402 AC XY: 29846 AN XY: 74284

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.442

Alfa AF: 0.436 Hom.: 6731

Bravo AF: 0.403

Asia WGS AF: 0.454 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.42

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: rs12598982; hg19: chr16-52536885;