rs8049149

chr16-52439207-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001080430.4(TOX3):c.*18G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,613,724 control chromosomes in the GnomAD database, including 14 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 0.0057 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (6 hom.)
• Consequence: TOX3 NM_001080430.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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=-0.86).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00571 (869/152248) while in subpopulation AFR AF= 0.0191 (794/41552). AF 95% confidence interval is 0.018. There are 8 homozygotes in gnomad4. There are 398 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 868 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX3	NM_001080430.4	c.*18G>A		3_prime_UTR_variant	7/7	ENST00000219746.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX3	ENST00000219746.14	c.*18G>A		3_prime_UTR_variant	7/7	2	NM_001080430.4	A2
TOX3	ENST00000407228.7	c.*18G>A		3_prime_UTR_variant	8/8	2		P2
TOX3	ENST00000566696.1	n.2213G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.00571 AC: 868 AN: 152130 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00138 AC: 344 AN: 248610 Hom.: 2 AF XY: 0.00105 AC XY: 141 AN XY: 134880

Gnomad AFR exome AF: 0.0193

Gnomad AMR exome AF: 0.000956

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.0000533

Gnomad OTH exome AF: 0.000497

GnomAD4 exome AF: 0.000547 AC: 799 AN: 1461476 Hom.: 6 Cov.: 30 AF XY: 0.000469 AC XY: 341 AN XY: 727022

Gnomad4 AFR exome AF: 0.0201

Gnomad4 AMR exome AF: 0.000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.000978

GnomAD4 genome AF: 0.00571 AC: 869 AN: 152248 Hom.: 8 Cov.: 32 AF XY: 0.00535 AC XY: 398 AN XY: 74424

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00409 Hom.: 0

Bravo AF: 0.00632

Asia WGS AF: 0.000866 AC: 3 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	5.0
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8049149; hg19: chr16-52473119;