dbSNP rs8049149: TOX3:c.*18G>A (chr16-52439207-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0130

Variant links:

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]

TOX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 869 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX3	NM_001080430.4 link	c.*18G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000219746.14	NP_001073899.2	O15405-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TOX3	ENST00000219746 link	c.*18G>A	3_prime_UTR_variant	Exon 7 of 7	2	NM_001080430.4	ENSP00000219746.9	O15405-1
TOX3	ENST00000407228 link	c.*18G>A	3_prime_UTR_variant	Exon 8 of 8	2		ENSP00000385705.3	O15405-2
TOX3	ENST00000566696.1 link	n.2213G>A	non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00571

AC:

868

AN:

152130

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00105

AC XY:

141

AN XY:

134880

show subpopulations

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.:

Cov.:

AF XY:

0.000469

AC XY:

341

AN XY:

727022

show subpopulations

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.:

Cov.:

AF XY:

0.00535

AC XY:

398

AN XY:

74424

show subpopulations

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.:

Bravo

AF:

0.00632

Asia WGS

AF:

0.000866

AC:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over