16-52454795-C-T

Position:

• chr16-52454795-C-T

Variant summary

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

The NM_001080430.4(TOX3):​c.409-4249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,036 control chromosomes in the GnomAD database, including 40,909 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 0.72 (40909 hom., cov: 31)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.409-4249G>A		intron_variant		ENST00000219746.14	NP_001073899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.409-4249G>A		intron_variant		2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.394-4249G>A		intron_variant		2		ENSP00000385705.3
TOX3	ENST00000563091.1	c.301-4249G>A		intron_variant		4		ENSP00000457401.1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110091 AN: 151916 Hom.: 40862 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.725 AC: 110192 AN: 152036 Hom.: 40909 Cov.: 31 AF XY: 0.721 AC XY: 53586 AN XY: 74282

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.703

Alfa AF: 0.651 Hom.: 11985

Bravo AF: 0.743

Asia WGS AF: 0.815 AC: 2829 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.34

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: rs1420546; hg19: chr16-52488707;