NM_001080430.4:c.88-36414G>A

Variant names:

• chr16-52504988-C-T
• rs12600239
• NM_001080430.4:c.88-36414G>A

Variant summary

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

The NM_001080430.4(TOX3):​c.88-36414G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,980 control chromosomes in the GnomAD database, including 4,995 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 0.25 (4995 hom., cov: 31)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	NM_001080430.4	MANE Select	c.88-36414G>A		intron	N/A	NP_001073899.2
	TOX3	NM_001146188.2		c.75+14418G>A		intron	N/A	NP_001139660.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	ENST00000219746.14	TSL:2 MANE Select	c.88-36414G>A		intron	N/A	ENSP00000219746.9
	TOX3	ENST00000407228.7	TSL:2	c.75+14418G>A		intron	N/A	ENSP00000385705.3
	TOX3	ENST00000563091.1	TSL:4	c.-21-36414G>A		intron	N/A	ENSP00000457401.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38092 AN: 151862 Hom.: 4986 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.251 AC: 38132 AN: 151980 Hom.: 4995 Cov.: 31 AF XY: 0.254 AC XY: 18825 AN XY: 74254

African (AFR) AF: 0.182 AC: 7556 AN: 41476

American (AMR) AF: 0.285 AC: 4346 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2125 AN: 5124

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4810

European-Finnish (FIN) AF: 0.290 AC: 3055 AN: 10542

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17783 AN: 67972

Other (OTH) AF: 0.273 AC: 576 AN: 2108

Alfa AF: 0.256 Hom.: 631

Bravo AF: 0.252

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.74
PhyloP100		-0.29
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: rs12600239; hg19: chr16-52538900;