chr16-52493370-T-A

Variant names:

• chr16-52493370-T-A
• rs7188610
• NM_001080430.4:c.88-24796A>T

Variant summary

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

The NM_001080430.4(TOX3):​c.88-24796A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,092 control chromosomes in the GnomAD database, including 3,160 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 0.19 (3160 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080430.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	NM_001080430.4	MANE Select	c.88-24796A>T		intron	N/A	NP_001073899.2	O15405-1
	TOX3	NM_001146188.2		c.76-24796A>T		intron	N/A	NP_001139660.1	O15405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	ENST00000219746.14	TSL:2 MANE Select	c.88-24796A>T		intron	N/A	ENSP00000219746.9	O15405-1
	TOX3	ENST00000912163.1		c.88-24796A>T		intron	N/A	ENSP00000582222.1
	TOX3	ENST00000873102.1		c.88-24796A>T		intron	N/A	ENSP00000543161.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28557 AN: 151972 Hom.: 3153 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.188 AC: 28586 AN: 152092 Hom.: 3160 Cov.: 32 AF XY: 0.186 AC XY: 13865 AN XY: 74350

African (AFR) AF: 0.287 AC: 11904 AN: 41446

American (AMR) AF: 0.147 AC: 2239 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1755 AN: 5166

South Asian (SAS) AF: 0.125 AC: 603 AN: 4822

European-Finnish (FIN) AF: 0.136 AC: 1442 AN: 10598

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9339 AN: 67996

Other (OTH) AF: 0.193 AC: 408 AN: 2116

Alfa AF: 0.0442 Hom.: 30

Bravo AF: 0.195

Asia WGS AF: 0.215 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.91
DANN	Benign	0.49
PhyloP100		-0.92
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: rs7188610; hg19: chr16-52527282;