NM_014729.3:c.412-26539A>G

Variant names:

• chr8-58878344-T-C
• rs765587
• NM_014729.3:c.412-26539A>G

Variant summary

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

The NM_014729.3(TOX):​c.412-26539A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,174 control chromosomes in the GnomAD database, including 3,553 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 0.20 (3553 hom., cov: 32)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 5 publications found

Genes affected

TOX (HGNC:18988): (thymocyte selection associated high mobility group box) The protein encoded by this gene contains a HMG box DNA binding domain. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. This protein may function to regulate T-cell development.[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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.412-26539A>G		intron_variant	Intron 3 of 8	ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.412-26539A>G		intron_variant	Intron 3 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31150 AN: 152056 Hom.: 3550 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0554

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.205 AC: 31171 AN: 152174 Hom.: 3553 Cov.: 32 AF XY: 0.202 AC XY: 15007 AN XY: 74408

African (AFR) AF: 0.290 AC: 12020 AN: 41510

American (AMR) AF: 0.172 AC: 2627 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3466

East Asian (EAS) AF: 0.0555 AC: 288 AN: 5190

South Asian (SAS) AF: 0.223 AC: 1079 AN: 4828

European-Finnish (FIN) AF: 0.139 AC: 1476 AN: 10594

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12146 AN: 67984

Other (OTH) AF: 0.190 AC: 401 AN: 2116

Alfa AF: 0.187 Hom.: 391

Bravo AF: 0.207

Asia WGS AF: 0.161 AC: 560 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.97
DANN	Benign	0.74
PhyloP100		-1.2
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: rs765587; hg19: chr8-59790903;